Can Chlamydia Be Transmitted Again With the Same Partner
J Infect Dis. 2011 Feb i; 203(3): 372–377.
The Role of Reinfection and Partner Notification in the Efficacy of Chlamydia Screening Programs
Janneke C.M. Heijne
1Institute of Social and Preventive Medicine, Academy of Bern, Bern, Switzerland
Christian L. Althaus
1Institute of Social and Preventive Medicine, Academy of Bern, Bern, Switzerland
Sereina A. Herzog
aneEstablish of Social and Preventive Medicine, Academy of Bern, Bern, Switzerland
Mirjam Kretzschmar
2Center for Infectious Disease Control, RIVM, Bilthoven
iiiJulius Center for Health Sciences and Primary Care, University Medical Heart Utrecht, Utrecht, The Netherlands
Nicola Depression
1Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
Received 2010 May 11; Accepted 2010 Oct 25.
Abstract
Repeated Chlamydia trachomatis infections afterward treatment are mutual. One reason is reinfection from untreated partners in ongoing sexual partnerships. Mathematical models that are used to predict the impact of screening on reducing chlamydia prevalence often do not incorporate reinfection and might overestimate the expected impact. We describe a pair compartmental model that explicitly incorporates sexual partnership duration and reinfection. The pair model predicts a weaker impact of screening when compared directly with a model that does not accommodate partnerships. Effective management of sex partners to prevent reinfection might need to exist strengthened in chlamydia control programs.
Repeated infections with Chlamydia trachomatis (chlamydia) afterwards handling are common [1, 2]. These are a potential obstacle for controlling chlamydia, the nearly mutual notifiable infection in the Us [3]. Batteiger et al used genotyping and sexual histories to show that a fraction of echo infections amongst young women were reinfections from an untreated sex partner within ongoing partnerships [1]. Other reasons included infections from subsequent partners, persistent infection, and failure to receive treatment [i]. Screening to identify and care for asymptomatic cases is the intervention most often recommended to reduce chlamydia prevalence and the incidence of female complications [three]; repeated episodes of pelvic inflammatory disease increment the risk of infertility [four]. High levels of successful notification of sex activity partners and adherence to handling and prevention advice might be an of import component of chlamydia control strategies. In practice the contributions of screening and partner notification to chlamydia command cannot be disentangled.
Mathematical modeling is a tool for understanding the manual and spread of infections in populations. Both individual-based [five] and compartmental models [six–9] have been used to predict the impact of chlamydia screening interventions. In published compartmental models, partnerships have non been incorporated explicitly and contacts are assumed to exist instantaneous [6–9]. These models therefore cannot explore the role of partner notification as part of the screening strategy [ten]. Information technology is often assumed that omitting this feature does non matter, because adding partner notification would outcome in an even greater subtract in predicted prevalence [viii]. However, if contacts are instantaneous, reinfection within partnerships cannot occur.
The objective of this report was to explore the specific role of chlamydial reinfection in ongoing partnerships in an intervention that includes both screening and partner notification. To allow direct comparison with a model that assumes instantaneous partnerships, we adult a pair compartmental model, which explicitly incorporates ongoing partnerships. Both models were calibrated to the same baseline prevalence by irresolute the transmission parameter, then the number of new cases per unit of time was the same in both. Nosotros then compared the bear on of different screening and partner notification strategies.
METHODS
Description of the Models
The pair model was based on work past Kretzschmar and Dietz [11] to study man immunodeficiency virus infection in men who have sex with men. We adjusted the model for heterosexual contacts among young adults and incorporated a susceptible-infected-recovered-susceptible (SIRS) construction (Effigy 1A; Appendix). In the model, transmission tin can simply occur in a pair of a susceptible and an infected private (SI). Every partnership starts with an episode of unprotected sexual intercourse with subsequent unprotected contacts once a calendar week (ϕ), consistent with published data [12]. This allows the duration of partnerships in the model to be compared with those in empirical studies that define the start of partnerships with a sex activity act.
Schematic overview of the chlamydia infection procedure in a pair model that allows for reinfection in ongoing partnerships (A) and in a standard model in which partnerships are instantaneous and reinfection is not incorporated (B). In the pair model, a compartment consists of a pair of 2 individuals which tin be susceptible (S), infected (I), or recovered (R). The pair germination process is independent of the infection process and is therefore not shown in this figure. Transmission can merely occur in a pair including a susceptible and an infected private (SI) with rate βϕ (β denotes the transmission probability per sex act and ϕ the frequency of sexual practice acts, indicated in red). Afterward chlamydial infection, an individual can clear the infection naturally (with charge per unit ε per year, indicated in black). Later on natural clearance, an individual is allowed for a duration of one/γ years (indicated in dark-green). An individual tin can also be screened and treated (with rate α per twelvemonth) and can notify his or her partner with probability q (indicated in blue). The partner ever accepts treatment. After treatment no immunity is assumed. In the standard model, the transmission parameter λ is a combination of the number of new partners per year and the transmission probability per partnership.
The duration of the infectious period (1/ε) of chlamydia is assumed to exist one twelvemonth. This takes into business relationship that about infections are asymptomatic and persist for >1 twelvemonth [thirteen, fourteen] but some infections are shorter considering symptomatic individuals visit health services and are treated. We assumed a short period of immunity after clearance (1/γ = 3 months) [thirteen].
Every private tin can receive screening (at rate α per year) using a test with perfect sensitivity. Everyone with a positive test accepts treatment, which is e'er effective. Subsequently treatment no amnesty is causeless [half dozen]. The current partner of an infected individual can exist notified with probability q, where the partner always accepts treatment. Partner notification is defined as the successful search and handling of the current partner and adherence to a period of abstinence until infection has cleared.
We assumed that individuals have on boilerplate 1.5 new partners per yr [eight] and that 70% of persons are in a partnership at any time, based on published data [12]. This corresponds to a pair germination rate (ρ) of 5.0/twelvemonth and an average elapsing of a partnership (1/σ) of 0.47 years. We assumed a baseline chlamydia prevalence of three.5% (the average among 15–24-years-olds in Regan et al [8]) and adjusted the transmission probability (β) to achieve this, resulting in a transmission probability per sex human action of 0.10. Nosotros assumed all parameters to be the same for males and females (a sensitivity analysis on this assumption was made). In the model, with prevalence at iii.five%, the percent of women repeatedly infected (a subsequent infection from the aforementioned or some other partner) 12 months after handling was 16.two%.
We compared the pair model with a standard SIRS model with instantaneous partnerships; reinfection inside the aforementioned partnership cannot occur and partner notification cannot be explored (Figure 1B; Appendix). The durations of immunity and the infectious flow are the same in both models. The transmission parameter (λ) is obtained by also assuming iii.5% preintervention steady state prevalence and 1.5 new partners per year, which gives a transmission probability per partnership of 0.seventy [15]. In both models the number of new infections per unit of fourth dimension (incidence) is the same. The number of people screened per year is therefore the aforementioned in both models.
Analyses
We implemented screening for 5 years. We estimated the impact of screening and partner notification from the preintervention steady state prevalence in the pair model and the bear upon of screening lone in the standard model. We calculated the difference between the predicted relative reduction in chlamydia prevalence in the standard model and in the pair model at unlike levels of partner notification. We then estimated the level of successful partner notification that is necessary in a model with reinfection to achieve the same reduction in prevalence equally in the model without reinfection; nosotros call this the bespeak of equality. Finally, nosotros examine the effect of changing the elapsing of amnesty after natural clearance on the point of equality for a stock-still screening charge per unit of 0.2/year. A sensitivity analysis of other parameter values was besides conducted (Appendix).
RESULTS
For a given screening rate, the turn down in chlamydia prevalence after 5 years is more than pronounced in a model with instantaneous partnerships in which reinfection cannot occur (standard model) compared with the pair model that allows for reinfection (Effigy 2A). Partner notification increases the impact of the intervention in the pair model because reinfection of treated cases from infected partners in ongoing partnerships is prevented, but this does not necessarily consequence in a greater impact of screening than the standard model (Figure 2A).
Impact of screening men and women for five consecutive years on chlamydia prevalence. A, Chlamydia prevalence in a pair model that allows for reinfection in the absenteeism (greyness line) or presence of partner notification (PN) (gray dashed line) and in the standard model (blackness line). B, Difference in the estimated relative impact of screening of the ii models in the absence of PN (black line) and in the presence of dissimilar levels of PN (greyness lines; lighter gray indicates higher levels of PN). The straight black line shows the point of equality, the level of PN needed in the pair model that allows for reinfection to estimate the same bear upon of screening as the standard model. C, Point of equality for dissimilar assumptions of the duration of immunity after natural clearance of chlamydia for a screening rate of 0.2/year. For all levels of immunity, the transmission probability per sex human activity (pair model) and the transmission parameter (standard model) is calibrated to a iii.5% baseline prevalence. The scenario used in A and B is indicated with a blackness dot.
The biggest difference in predicted impact between the 2 models is observed for screening rates between 0.1 and 0.iv per yr (Effigy 2B). As the screening charge per unit increases, the bear upon of partner notification becomes less apparent. With no partner notification (Figure 2B), the peak difference in the affect of screening betwixt the models is 8.2% at a screening charge per unit of 0.25/year. This corresponds to a population where each individual is screened on average every 4 years. With increasing partner notification, the impact of screening in the pair model comes shut to estimates from the standard model; the point of equality occurs when ∼30% of electric current partners are successfully notified (Figure 2B). At higher partner notification levels, the bear upon of screening is greater in the pair model than in the standard model.
Nosotros explored the style in which the duration of immunity after natural clearance affects the level of partner notification at the betoken of equality (Figure 2C). When no amnesty is causeless in either model, a lower level of partner notification is needed to reach the point of equality. The longer the duration of immunity after natural clearance, the more than partner notification is needed to weigh the effect of reinfection after screening.
We performed a sensitivity analysis of the point of equality for other parameters in all plausible ranges (Appendix). Under the ranges investigated, the model with reinfection always estimates a less pronounced impact of screening than the standard model, and the level of partner notification at the signal of equality tin differ betwixt 4% and 39%. When merely 1 sex is screened the magnitude of the departure between the models is like, with the peak screening rate shifted toward higher levels and a slightly lower point of equality. Increasing the duration of screening from 5 to 20 years resulted in a peak difference between the 2 models shifted to lower screening rates and a slightly lower point of equality.
Discussion
This study shows that, when reinfection by the current partner after screening and treatment for chlamydia is taken into account in a pair model, the touch on of screening on reducing chlamydia prevalence is less pronounced than in a standard model that allows only for instantaneous partnerships and in which reinfection cannot happen. Even when partner notification is included in a screening strategy in the pair model, the bear on on chlamydia prevalence tin exist less than that of screening solitary in a standard model. This indicates that it is non valid to state that the predictions from a standard model of chlamydia manual are bourgeois [8, ten]; in some cases such estimates tin fifty-fifty be optimistic. This study supports the theoretical proposal that partnerships should exist incorporated explicitly in mathematical models that assume that partner notification is part of a strategy for controlling chlamydia transmission [ten].
This modeling study is intended to be illustrative rather than predictive so that nosotros could focus specifically on the role of reinfection. Nosotros therefore made several simplifying assumptions. Historic period structure was not included. Homogeneous mixing is causeless, merely nosotros hypothesize that if a certain fraction of the population has higher partner change rates and shorter partnerships, these individuals would have a higher probability of repeated infection, and this would make notification of current partners less effective. We also causeless men and women to be the same; shortening the duration of the infectious flow in men resulted in an even higher point of equality. We did non consider persistent infection because we assumed 100% treatment efficacy. The repeat infection charge per unit in the pair model was, however, consistent with published studies [2]. For all other parameters, within the ranges studied, the pair model ever estimates a less pronounced affect of screening compared with the standard model (Appendix).
At that place is ongoing give-and-take about the role of immunity in chlamydial infections [6]. We prove that when immunity after natural clearance exists, more partner notification is needed to counterbalance the effect of reinfection; to achieve the aforementioned baseline steady land prevalence, the transmission probability per sexual activity human action in a model with immunity must be higher than in a model without immunity, if all other parameters are assumed equal. The probability of reinfection after screening is therefore higher in a model with amnesty, and more than partner notification is needed to counterbalance this. If immunity also exists after screening and treatment, less reinfection will occur subsequently screening and lower partner notification levels are needed.
The accented difference in the impact of screening on chlamydia prevalence betwixt the ii models was modest. In a large population, however, this can translate into a large number of episodes of reinfection inside ongoing partnerships. Excluding reinfections from a standard model might therefore improve cost-effectiveness in favor of screening, especially because the risk of infertility increases with each subsequent episode of pelvic inflammatory disease [4].
Our results have implications for the design of chlamydia command strategies. We plant that, in a model with reinfection, ∼30% of current sex partners demand to be notified to counterbalance the effect of reinfection. Although this sounds modest, information technology requires total compliance with identifying and informing a sexual practice partner, treatment to be given and taken, and abstinence from sexual intercourse until infection has cleared. Standing high chlamydia prevalence, even afterwards regular repeated screening, early treatment, and partner notification efforts, suggests that this is difficult to achieve in exercise [i]. Additional empirical studies should seek to improve partner notification effectiveness in exercise, and additional modeling efforts should focus on understanding the most promising partner notification strategies. Our study suggests that effective direction of sexual practice partners to prevent reinfection might need to exist strengthened in chlamydia control programs.
Financial support: Swiss National Science Foundation (grants 320030_118424 and PDFMP3_124952 to J.C.Yard.H. and Due south.A.H.); UK National Found for Health Inquiry (NIHR) Health Technology Cess program (projection 07/42/02 to C.50.A.). The views and opinions in this article are those of the authors and practice non necessarily reverberate those of the funders.
APPENDIX.
Description of the Model
We have adult a pair model with a SIRS structure. The model explicitly describes the formation of pairs (P) and the dissolution of pairs into singles (X) [sixteen]. The model stratifies the population by sex with the labels f and m describing females and males, respectively. The male and female populations are assumed to be of equal size; thus, Northwardf =Northwardyard. The infection states of the model are susceptible (S), infected (I), and recovered (R).
In the notation of singles, the showtime subscript defines the sex of the unmarried, and the second subscript defines the infection state. In the annotation of pairs, the outset subscript defines the land of infection of the female and the second subscript defines the state of infection of the male. Thus P SI is a pair with an uninfected female and an infected male, while P IS is a pair with an infected female and an uninfected male. The stardom between P SI and P IS is but important when different screening rates are assumed for females and males, or when there are sexual practice differences in the behavioral or infection parameters. For the modeling results and Figure one described in the principal text, we assume that all parameters are the aforementioned in both sexes. However, we performed a sensitivity analyses in this appendix in which we screen only 1 sex.
Every infected individual tin be screened at a charge per unit α per year (with α f being the screening rate for females and α thou that for males). When an individual is screened, the partner can be notified with a probability q. A person tin can clear the infection naturally with charge per unit ε (with 1/ε f being the duration of the infectious catamenia for females and 1/ε k that for males). After natural clearance a period of immunity (1/γ) is assumed. Pairs are formed with a pair formation rate ρ per year and divide with rate σ per year. The separation rate can be calculated as the average per capita number of new partners per year divided by the percentage of people in a partnership. The pair formation charge per unit can be calculated as the boilerplate per capita number of new partners per year divided past the percentage of persons who are single. Transmission tin can occur only in partnerships, with ϕ being the number of sex acts per week, and β existence the transmission probability per sexual activity human activity. Every partnership starts with a unmarried sexual contact by assuming that, on formation of a partnership between a susceptible and an infected individual, they become a pair of infected individuals with probability β, and they remain a pair of an infected and a susceptible individual with probability ane – β until the next sex activity act [sixteen].
The SIRS pair model is described by the following set of differential equations:
The number of singles is given every bit X =Xf +Tenchiliad =Xf, S +Xf, I +Xf, R +Tenchiliad, S +Xg, I +Tenone thousand, R, and the total population size tin can be expressed as Due north =Xf +Xthou + two(P SS +P SI +P SR +P IS +P II +P IR +P RS +P RI +P RR).
The differential equations of the standard SIRS is described by the following prepare of differential equations:
The manual parameter (λ) is a combination of the manual probability per partnership times the number of new partners per year. The transmission parameter is adjusted to obtain the same baseline prevalence as in the pair model.
Sensitivity Analyses
In the main text we showed that in a model that allows for reinfection, a substantial amount of successful partner notification is needed to judge the same impact of screening as in a standard model that does not let for reinfection (point of equality). In the sensitivity analyses, we explore the point of equality for all parameters used in all plausible parameter ranges. Because the signal of equality is hardly afflicted by the screening charge per unit (Figure 2B), the sensitivity analyses is performed for a screening rate of 0.ii/year.
For all parameters ranges examined, nosotros suit the manual parameter (β and λ) to obtain a baseline steady-state preintervention prevalence of 3.5%. We only explored the parameter ranges for which nosotros could obtain a transmission probability β between 0 and 1.
In the main text it is shown that when no immunity is assumed in the model, the point of equality is at its lowest (Figure 2C). Therefore, and for simplicity, some parts of the analyses are done using a model without immunity after natural clearance (SIS model). Figures showing the results of the sensitivity analyses are available from the authors on request.
Duration of Infectious Period.
If the duration of the infectious menses is varied betwixt 0.v and two years in a Sis model, the level of partner notification at the betoken of equality decreases from 32.four% to 17.3%. Thus, with increasing duration of the infectious period, less partner notification is needed to counterbalance the effect of reinfection. This is because increasing the infectious flow results in a lower manual rate per sex act, which results in lower reinfection rates. Therefore, less partner notification is needed to reach the point of equality.
We besides explored a scenario in which men take a shorter infectious period than women. Shortening the duration of the infectious menstruation in men to half a year and keeping the infectious period of women i year resulted in a higher level of partner notification at the point of equality (37.0%).
Behavioral Parameters.
Nosotros explored the effect of changing both the percentage of people in a partnership from 10% to 90% and the new number of partnerships per year from ane partner up to four partners per twelvemonth at steady country in a Sister model. Inside the ranges explored, the level of partner notification at point of equality varies between 4.3% and 39.3%. The number of new partners per twelvemonth influences the estimates more than the percentage of people in a partnership. A higher number of new partnerships per year volition automatically result in shorter partnership durations. Equally a issue, both models predict near the same touch on of screening, and little partner notification is needed to attain the point of equality. When the new number of partners per year is low, and the percentage of people in a partnership increases, the duration of the partnerships volition automatically increment, and the differences between both models get more apparent. As a consequence, more partner notification is needed to estimate the same bear on of screening in the pair model that allows for reinfection compared with a standard model.
Transmission Parameters.
In all analyses so far, we kept the baseline preintervention steady-state prevalence at 3.v%. Therefore, we also explored the issue of a different baseline prevalence on the point of equality in a Sis model. For every value of the baseline prevalence studied (0.5%–15%), we adjusted the manual parameter β and λ. In the pair model, this tin also be seen as keeping β constant but changing the frequency of sex activity acts between once every 7.3 and 0.half dozen days. For a baseline prevalence of 0.5%, the level of partner notification at the point of equality is 30.3%, and this steadily decreases to a level of nine.ane% when the baseline prevalence is increased to 15%. With increasing baseline prevalence, it becomes more probable that both partners are infected, and hence partner notification becomes more than efficient. Therefore, less partner notification is needed to reach the same touch on of screening without reinfection.
Screening.
We as well explored the results of screening just 1 sex for 5 consecutive years. In general, when only one sex is screened, the impact of screening is less compared with when both sexes are screened. The magnitude of the difference in the predicted impact of screening between the model that assumes instantaneous partnership and the pair model is more or less similar as when both sexes are screened (Figure 2B). However, the peak deviation between the models is shifted toward college screening strategies. The partner notification at point of equality is slightly lower (26.v%) than when both sexes are screened.
In the master text, screening is implemented for v consecutive years. Increasing the duration of screening from v to 20 years resulted in a peak divergence between the 2 models shifted toward lower screening rates and a slightly lower partner notification level at the point of equality (23.9%).
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071108/
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