AN INSIGHT INTO THE DRUG RESISTANCE PROFILE AND MECHANISM OF DRUG RESISTANCE IN NEISSERIA GONORRHOEAE

TABLE OF CONTENT

Title Page                                                                 i

Certification                                                     ii

Acknowledgement                                            iii

Abstract                                                           IV

CHAPTER ONE

Introduction

CHAPTER TWO

Characteristic of Neisseria Gonorrhea

CHAPTER THREE

Epidemiology

Mechanism of Drug Resistance

CHAPTER FOUR

Conclusion

Recommendation

Reference  

ABSTRACT

        Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neisseria Gonorrhea is considered to be most important, because of emerging antibiotic resistance strains that compromise the effectiveness of treatment of the disease. Gonococci infections are usually treated with single – dose therapy with an agent found to cure above 95 percent of each case, but unfortunately Neisseria gonorrhea has developed resistance to most of the antibiotic used against it, which can be categorized into pre-quinolone, quinolone and post – quinolone era.

        Among the anti-biotic available so far, the third generation “cephalosporin has also be safely recommended as first line therapy for gonorrhea globally;

INTRODUCTION

        Despite the recent advances in diagnosis, surveillance and treatment, sexual transmitted disease (STDs) remain one of the leading diseases throughout the world. Increased promiscuity and onset of sexual activity at an early age are two important contributing factors to the spread of sexual transmitted disease.  Neisseria gonorrheae (also known as the gonococcus) colonizes primarily in the human genital urinary tract, giving rise to the sexually transmitted infection gonorrhea.  It cause both symptomatic and asymptomatic genital and extra genital tract infections.  Disease caused by this organism is a significant public health problem despite continual advances in treatment (Tanaka and Reyn et al, 2004).

World wide, there is an estimated 62million new cases a year, with an average of 22miilion cases at any given time (WHO, 1992).  N. gonorrhea inhabits mainly mucosal surface of the urethra in males and the cervix in females.  As the signs and symptoms of infection are often absent or obscure complication such as pelvic inflammatory disease (PID), infertility, entopic pregnant woman may lead to crucial perforation and blindness in the newborn. Gonococci infection have also been documented to facilitate acquisition and transmission of HIV and HPV infection (Hunter et al. 1990).  Asymptomatic infections by N. gonorrhoeae largely contribute to the persistence and transmission of disease in a community. (Hunter et, al.1990).

Therefore, to eliminate N. gonorrhea infection and in turn to control HIV and HPV infection it is important not only to screen high – risk population but also to treat them immediately with most effective drugs.  Control of gonococci infection has relied on effective single – dose antibiotic therapy given at the initial clinical visit, prior to any knowledge of the organism’s susceptibility pattern.  In the recent past, there has been an alarming increase in the number of isolate of N. gonorrhea resistance to commonly used drugs.  (Chaudhry et al, 2002).  Surveillance is therefore, necessary to understand on going resistance trends and to ensure the success of any therapy.

The irrational and injudicious use of antibacterial agents especially in the developing countries is encouraging this trend and the situation is expected to worsen unless appropriate steps are initiated. This resistance of the gonococcus to antibiotics has been the cause of much concern in recent years and has been the subject of extensive investigation.  The present review summarizes and trends to drug resistance in N. gonorrhoeae, mechanism of drug resistance and discusses the treatment regime.  In addition, the need to look for new and alternative antibacterial agent is also emphasized.

CHARACTERISTICS OF NEISSERIC GONORHOEAE

        Neisseria gonorrhoeae is a gram – negative diplococci and is know to infect human only.  It is closely related to and probably derived from Neisseria meningitides, but has because highly adapted to survival in the genital tract.  It is transmitted by human-to- human contact and survives poorly outside the human   body.  Neisseria gonorrhoea is a very successful pathogen as it can evade or adapt to host defenses persist without severally damaging the host, and be transmitted to and infect other hosts, thereby maintaining itself.

 Particularly in women, gonococci may produce only mildly symptomatic or asymptomatic disease.  This adaptation allows the organism to persist and disseminate over long periods (Brunham and Plummer 1993).

The most important characteristic of Neisseria gonorrhoeae, in the content of antimicrobial resistance pattern are its phenotypic and genotypic variability which enable it to evade the host response.  Phenotypic variability occurs through differential expression of existing parts of the genome.  Genotypic variation is achieved by incorporation of new genetic material, which can be acquired either by conjugation are transformation. 

It is because of this feature that N. gonorrhoeae has acquired penicillin’s producing plasmids. Another important feature of N. gonorrhoeae is its antigenic variability.  This helps the bacterium to survive in its limited host i.e. human.  Antigenic variability of N. gonorrhoeae is partially due to its ability to acquire genetic material from related organism.  (Sarafian and Knapp 1989).

EPIDEMIOLOGY   

Single dose therapy for Neisseria gonorrhoeae infection bas become the norm in most of the countries through out the world.  The basic reason behind this is that single close therapy is most effective and assures adequate treatment.  World Health Organization (WHO) recommendations for selecting any treatment for gonorrhoea.  States that the antimicrobial prescribed should be such that the cure rate is about 95 percent (Quinn, 1996). More over, during the past few year N. gonorrhoeae has started developing resistance against most of the antimicrobials that are described for its therapy.  Therefore, surveillance of the antimicrobial resistance becomes very important in monitoring the emergence and spread of resistance and in planning appropriate treatment regimens.     

Gonorrhea is a disease mainly found in resource poor settings where laboratory facilities are limited or unavailable. Due to this reason, culture and antimicrobial susceptibility testing of N. gonorrhoeae is hardly done in developing countries. Developed countries had collected the data in a proper manner due to availability of adequate resources which help in monitoring resistance data obtained from developing countries are mainly from point presence studies, which can not be use to follow the trends.  Such epidemiological study need to be done at a regular basis because the prevailing strains of the bacteria and their antimicrobial susceptibility profiles keep on changing. (Tapsall 2001).