Core Groups, Resistance and Rebound in Gonorrhoea
Core Groups, Resistance and Rebound in Gonorrhoea
Background Genital tract infections caused by Neisseria gonorrhoeae are a major cause of sexually transmitted disease worldwide. Surveillance data suggest that incidence has increased in recent years after initially falling in the face of intensified control efforts.
Objectives The authors sought to evaluate the potential contribution of antimicrobial resistance to such rebound and to identify optimal treatment strategies in the face of resistance using a mathematical model of gonorrhoea.
Methods The authors built risk-structured 'susceptible–infectious–susceptible' models with and without the possibility of antibiotic resistance and used these models as a platform for the evaluation of competing plausible treatment strategies, including changing antimicrobial choice when resistance prevalence surpassed fixed thresholds, random assignment of treatment and use of combination antimicrobial therapy.
Results Absent antimicrobial resistance, strategies that focus on treatment of highest risk individuals (the so-called core group) result in collapse of disease transmission. When antimicrobial resistance exists, a focus on the core group causes rebound in incidence, with maximal dissemination of antibiotic resistance. Random assignment of antimicrobial treatment class outperformed the use of fixed resistance thresholds with respect to sustained reduction in gonorrhoea prevalence.
Conclusions Gonorrhoea control is achievable only when core groups are treated, but treatment of core groups maximises dissemination of antimicrobial-resistant strains. This paradox poses a great dilemma to the control and prevention of gonorrhoea and underlines the need for gonococcal vaccines.
Genital tract infection due to Neisseria gonorrhoeae (NG) is an important sexually transmitted infection in North America, both in terms of the absolute number of individuals infected annually and in terms of the cost and burden of illness associated with disease sequelae, including pelvic inflammatory disease and its complications in women, epididymo-orchitis and prostatitis in men, ophthalmic disease in neonates, enhanced risk of HIV transmission and acquisition, and rarely disseminated infection.
Starting from the late 1970s and early 1980s, the incidence of gonorrhoea had decreased sharply, and by an order of magnitude, in the USA and Canada. This represented an important public health success, and one that was predicted by mathematical models. Models demonstrate that a pathogen such as NG, characterised by a relatively brief duration of infectiousness, is strongly dependent on individuals with high rates of sex partner change or concurrency (the so-called core groups) for continued propagation such that antibiotic treatment of core groups precipitates a rapid decline in the incidence and prevalence of infection in the population as a whole.
Cases of gonorrhoea persist, however, despite targeted treatment of core groups, which has been standard and largely effective for decades. Since 1997, incidence rates have remained stable but high in the USA, while rates have been increasing in Canada, nearly doubling in the Canadian province of Ontario, for example, where rates have risen from 15 to 25 cases per 100 000 population between 1997 and 2007. Given that the target goal for gonorrhoea incidence in the USA was a reduction to 19 cases in 100 000 people by 2010 and the actual incidence was 118.9 cases in 100 000 people in 2007, there is a clear cause for concern.
Many factors likely contribute to the increasing numbers of infection in the last decade, including 'risk compensation' in sexual behaviour, due to perceptions of decreased risk and declining fear of HIV spread and the development of antimicrobial resistance in NG. Multidrug-resistant NG isolates are becoming increasingly common, and there have been reports of rapidly emerging resistance to 'single-dose' therapies (including fluoroquinolones and third-generation cephalosporins), suggesting that resistance might play a larger role in the dissemination of NG than previously acknowledged, specifically with regard to the rate of rebound infection.
While a focus on core groups might be the optimal means for controlling NG at the population level in the absence of antimicrobial resistance, few investigators have considered the impact that core groups could have in propagating resistant strains, thus paradoxically undermining disease control efforts. We sought to use a simple mathematical disease transmission model to evaluate the impact of core groups on the dissemination of antimicrobial resistance and to use modelling as a platform to explore the potential impact of competing antibiotic management strategies, with and without adjunctive laboratory testing, on the long-term control of NG.
Abstract and Introduction
Abstract
Background Genital tract infections caused by Neisseria gonorrhoeae are a major cause of sexually transmitted disease worldwide. Surveillance data suggest that incidence has increased in recent years after initially falling in the face of intensified control efforts.
Objectives The authors sought to evaluate the potential contribution of antimicrobial resistance to such rebound and to identify optimal treatment strategies in the face of resistance using a mathematical model of gonorrhoea.
Methods The authors built risk-structured 'susceptible–infectious–susceptible' models with and without the possibility of antibiotic resistance and used these models as a platform for the evaluation of competing plausible treatment strategies, including changing antimicrobial choice when resistance prevalence surpassed fixed thresholds, random assignment of treatment and use of combination antimicrobial therapy.
Results Absent antimicrobial resistance, strategies that focus on treatment of highest risk individuals (the so-called core group) result in collapse of disease transmission. When antimicrobial resistance exists, a focus on the core group causes rebound in incidence, with maximal dissemination of antibiotic resistance. Random assignment of antimicrobial treatment class outperformed the use of fixed resistance thresholds with respect to sustained reduction in gonorrhoea prevalence.
Conclusions Gonorrhoea control is achievable only when core groups are treated, but treatment of core groups maximises dissemination of antimicrobial-resistant strains. This paradox poses a great dilemma to the control and prevention of gonorrhoea and underlines the need for gonococcal vaccines.
Introduction
Genital tract infection due to Neisseria gonorrhoeae (NG) is an important sexually transmitted infection in North America, both in terms of the absolute number of individuals infected annually and in terms of the cost and burden of illness associated with disease sequelae, including pelvic inflammatory disease and its complications in women, epididymo-orchitis and prostatitis in men, ophthalmic disease in neonates, enhanced risk of HIV transmission and acquisition, and rarely disseminated infection.
Starting from the late 1970s and early 1980s, the incidence of gonorrhoea had decreased sharply, and by an order of magnitude, in the USA and Canada. This represented an important public health success, and one that was predicted by mathematical models. Models demonstrate that a pathogen such as NG, characterised by a relatively brief duration of infectiousness, is strongly dependent on individuals with high rates of sex partner change or concurrency (the so-called core groups) for continued propagation such that antibiotic treatment of core groups precipitates a rapid decline in the incidence and prevalence of infection in the population as a whole.
Cases of gonorrhoea persist, however, despite targeted treatment of core groups, which has been standard and largely effective for decades. Since 1997, incidence rates have remained stable but high in the USA, while rates have been increasing in Canada, nearly doubling in the Canadian province of Ontario, for example, where rates have risen from 15 to 25 cases per 100 000 population between 1997 and 2007. Given that the target goal for gonorrhoea incidence in the USA was a reduction to 19 cases in 100 000 people by 2010 and the actual incidence was 118.9 cases in 100 000 people in 2007, there is a clear cause for concern.
Many factors likely contribute to the increasing numbers of infection in the last decade, including 'risk compensation' in sexual behaviour, due to perceptions of decreased risk and declining fear of HIV spread and the development of antimicrobial resistance in NG. Multidrug-resistant NG isolates are becoming increasingly common, and there have been reports of rapidly emerging resistance to 'single-dose' therapies (including fluoroquinolones and third-generation cephalosporins), suggesting that resistance might play a larger role in the dissemination of NG than previously acknowledged, specifically with regard to the rate of rebound infection.
While a focus on core groups might be the optimal means for controlling NG at the population level in the absence of antimicrobial resistance, few investigators have considered the impact that core groups could have in propagating resistant strains, thus paradoxically undermining disease control efforts. We sought to use a simple mathematical disease transmission model to evaluate the impact of core groups on the dissemination of antimicrobial resistance and to use modelling as a platform to explore the potential impact of competing antibiotic management strategies, with and without adjunctive laboratory testing, on the long-term control of NG.