Sexually Transmitted Diseases
Gonorrhoea is caused by Neisseria gonorrhoeae. It usually is characterized by purulent genital discharge, urethritis and dysuria. Infection also can be asymptomatic, especially in women. Asymptomatic carriers are more likely to transmit the disease than people with overt infections. Similarly, anorectal and pharyngeal infections, which are not uncommon in women and men who have sex with men, frequently remain asymptomatic but constitute a potential source of transmission. Global estimated incidence of gonorrhoea is 62 million infected people annually. Complications of the disease include epididymitis in men and PID in women, with subsequent risk of infertility and ectopic pregnancy. In about 1% of cases, the gonococcus becomes invasive and a bacteraemia develops, leading to disseminated gonococcal infection characterized by skin rash and asymmetrical septic polyarthritis. The most common manifestation of gonorrhoea in the newborn is purulent conjunctival infection (gonococcal ophtalmia neonatorum), which constitutes a medical emergency because blindness may rapidly ensue. The incidence of the disease has been greatly reduced by routine prophylactic administration of 1% silver nitrate eyedrops.
N. gonorrhoeae is a gram-negative diplococcus. Specific serological reactions serve to distinguish gonococci from other species of Neisseria and permit serogrouping of gonococcal strains. The gonococcal liposaccharide (LPS) consists of branched oligosaccharide chains whose antigenic heterogeneity constitutes the basis of interstrain differences. The bacterial envelope is traversed by long pili constituted of repeated peptide subunits (pilin) that are characterized by both antigenic and phase variations. Antigenic variations result from chromosomal rearrangements altering the expression of any one of several silent pilin genes. Phase variation (pi + to pil-) occurs when the rearrangement involves a defective pilin gene. The predominant protein in the gonococcal outer membrane is termed protein I. This protein, which exists in two allelic forms, PIA and PIB, forms anion-selective transmembrane channels through the outer membrane and thus functions as a porin (POR protein). It is possible to divide gonococci into at least 24 PIA serovars and 32 PIB serovars on the basis of antigenic determinants on protein I. The complete nucleotide sequence of N. gonorrhoeae has been determined.
The life cycle of the bacterium was studied using a variety of cell culture systems. These studies have shown that the bacterium not only adheres to the epithelial cells but also penetrates and transits across the epithelial layer and exits into the subepithelial space where the symptoms of the disease are actually elicited.
The lack of a suitable animal model and the considerable antigenic variability of the bacterium have hampered the development of a vaccine for gonorrhoeal disease. Attachment of gonococci to mucosal cells is mediated in part by the pili, and it was found that rabbit antibody to pili reduces attachment of the bacteria to mammalian cells. Pilin was therefore chosen as the most likely vaccine candidate and tested for efficacy in military recruits and in volunteers challenged urethrally. This approach was met with some success, but protection was strain-limited, due the high rates of antigenic variation of pili. Porin also was studied as a vaccine antigen but the induced anti-porin antibodies were not bactericidal. Identification of potential vaccine antigens will hopefully be helped by the availability of the complete genome sequence, allowing the search of candidate proteins with similarity to proteins important in immunity to other bacterial pathogens.