Impact of the 7 Valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Carriage of S. Pneumoniae in Healthy Jordanian Infants.

S. pneumoniae is one of the major bacterial causes of invasive disease, community acquired pneumonia and respiratory tract infections worldwide (Song, Oh et al. 2008). It causes meningitis, bacteraemia, otitis media, pneumonia and other infections. The resistance rate of this bacteria to antibiotics all over the world is increasing and the mortality rate globally have reached 2 million every year as reported by the WHO. Risk groups are mainly young children under 5 years of age, immune-deficient patients and elderly. There are 91 different serotypes of this infectious agent known worldwide. In the United States of America and Europe, research on S. pneumonia showed that over than 70-85% of all S. pneumoniae cases can be covered and prevented by the 7-valent pneumococcal conjugate vaccine (Prevenar (7v-PCV)). This percentage is different according to the country. In Jordan, this vaccine was introduced and licensed in January 2006 without any previous preliminary studies of the serotypes or capsular types found. Furthermore, there are no published data about the infections caused by Streptococcus pneumonia from Jordan. The total number of Jordanian population is estimated in 2007 to be 5,744 million inhabitants with birth rate 28 per 1000 and these people are concentrated in the capital of Amman (1.781 million), Irbid (629679) and Zarqa (819000). Of Jordanian inhabitants and according to WHO recent numbers of 2008, 37.1% are children below 15 years of age and 3.8% are over than 65 years of age, and total children below 5 years are estimated 2007 to be 917000. This means that the people at risk of pneumococcal infections is 40.9% of the total population. Furthermore, statistical data of the MOH reported an increase of non-meningococcal meningitis cases (without specification of the exact cause of meningitis) from 438 cases (incidence 10.2/ 100,000 population) in 1995 to 778 cases (incidence 14.5/ 100,000 population) in 2007. In 2005, 458 cases/ 747 cases (61%) were from Irbid city alone -north-; and this was 460 cases in 2007 from 778 cases with non meningococcal meningitis. The maximum number of cases with non-meningococcal meningitis was reported in years 2000 (1108 cases with an incidence rate of 22/ 100,000), and in 2003 (1079 cases with an incidence rate of 19.7/ 100,000). In 2007, 778 cases were reported in Jordan with non-meningococcal meningitis, 140 of these cases were from Amman and 490 were from Irbid alone and the rest are from the other parts in Jordan. If we consider as is known that 30% of these infections (non-meningococcal meningitis) are due to S. pneumonia. This means that 233 cases with S. pneumonia meningitis reported annually with 147 from Irbid and 42 cases from Amman which makes 189 cases (81% of all pneumococcal meningitis of Jordan occurring in Irbid and Amman).

Many factors have been identified to promote the clonal spread of multiresistant strains; such as places with high density of children as in DCC and orphanages. S. pneumonia, that are resistant to many antimicrobial agents. Extensive and often excessive use of antibiotics can promote the replacement of strains susceptible to antimicrobial agents by resistant ones (Garcia-Rodriguez and Fresnadillo Martinez 2002), (Pradier, Dunais et al. 1997). Despite adequate antibiotic treatment, morbidity and mortality due to pneumococcal disease remain high (Butler, Shapiro et al. 1999). Moreover, the increase of multidrug resistance among pneumococcal isolates hampers adequate treatment (Crook and Spratt 1998), (Klugman 1996), (Tomasz 1997). These strains are subsequently disseminated in the community by other contacts of colonized children, e.g., their siblings and parents. It is possible to limit the spread of some serotypes of S. pneumoniae by vaccination, but studies of the impact of immunization on colonization have yielded discrepant results (Dagan, Givon-Lavi et al. 2002), (Dagan, Melamed et al. 1996), (Dagan, Muallem et al. 1997), (Mbelle, Huebner et al. 1999). New pneumococcal conjugate vaccines have been shown to be effective against invasive diseases in young children (Black, Shinefield et al. 2000). Furthermore, a protective effect against respiratory tract infections such as (recurrent) otitis media has been observed (Black, Shinefield et al. 2000), (Eskola, Kilpi et al. 2001). Thus far, the 7-valent pneumococcal conjugate vaccine Prevenar (Wyeth) has been approved by the U.S. Food and Drug Administration and the European Committee on Proprietary Medicinal Products and is recommended by the U.S. Advisory Committee on Immunization Practices for the prevention of invasive diseases in children under 2 years of age. Recommendations are also made for older children at increased risk for invasive disease, such as those with human immunodeficiency virus infection and asplenia and those with increased risk for pneumococcal mucosal disease, such as children with recurrent acute otitis media. The effect of the 7-valent pneumococcal conjugate vaccine followed by a 23-valent polysaccharide vaccine in children aged 1 to 7 years with a history of recurrent acute otitis media was studied (Veenhoven, Bogaert et al. 2003). Clinically, no protective effect of the pneumococcal vaccines on recurrence of acute otitis media was found. At the nasopharyngeal level, however, a significant reduction of colonization with vaccine-type pneumococci was found after vaccination, whereas a simultaneous increase in colonization with non vaccine serotypes was observed (Veenhoven, Bogaert et al. 2003), (van der Linden, Al-Lahham et al. 2007). The spread of non-vaccine 19A penicillin resistant pneumococcal strains in the USA is a very serious development indeed, the children had to be treated with levofloxacin and one became partially deaf. With widespread of Prevenar use in Jordan this clone might appear (Pichichero and Casey 2007; Pichichero and Casey 2007). Recently, a Ph D study in Jordan showed that the resistance of penicillin G to S. pneumoniae isolated from healthy children in the kindergarten has reached to 92%. The efficacy of the 7v PCV to define the disease burden in the developing countries has been studied .

SIGNIFICANCE OF WORK

This research project has many dimensions including the following:

• The research project would give an idea about the effect of the vaccine that is given to the children, whether this would affect the incidence of IPD indirectly in the city of Ajlun compared to others.
• As a result of the first point, a governmental National program of vaccination of children will take place for the Jordanian children at specific age
• In addition, the resistance pattern of the isolates against 14 different antibiotics will be developed. High resistance rates will indicate that treatment with such an antibiotic is not efficient and we must use an alternative for the treatment. A precise result of the antibiotic resistance pattern could save money by prescribing antibiotics that are safe and effective, and would educate the Jordanian population about a better use of antimicrobials.
• Furthermore, Serotyping of S. pneumoniae isolates of all pneumococcal strains isolated in this study would give an idea about the coverage of the vaccine available and would answer the families question shall we vaccinate our children or not!! Why should we pay 85 JDs privately to vaccine since the coverage is less than 50% as an example. Here comes the question whether we should use the 13 va,lent vaccine of the same type, which is still under development. Carriage of S. pneumoniae in Jordan pediatrics below 5 was developed in the primary results of the carriage in Jordan and was 57%. if the carriage distribution in the Jordanian population has to do with specific serotypes, which are included in the 7-vPCV, then vaccination would be the best idea to prevent occurrence of the infection then decrease morbidity and later the mortality rate due to the infections of this pathogen. The northern of Jordan constitutes of more than 50% of all non-meningococcal infections.
• An appropriate vaccination program of specific areas and/or specific age groups in Jordan might decrease the distribution of this disease and in turn saving money.
• The results will obtain an insight into the effect of the pneumococcal conjugate vaccine on the genetic pneumococcal population structure.
• The research findings will later on improve the quality of different private and governmental laboratories in Jordan through personal contact and advising. By applying bioinformatics and the phylogeny from the data of resistance, serotyping and Multilocus Sequence Typing (MLST), global clonal relationship of the strains can be obtained from the data.