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# The natural history of syphilis. Implications for the transmission dynamics and control of infection

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Syphilis remains a significant cause of morbidity in many developing countries and in some areas within North America and Europe. Mathematical models of the transmission dynamics of sexually transmitted infections have provided insights of relevance both to the interpretation of observed epidemiological patterns and to the design of control programs. Their use for the study of syphilis has been limited to date. GOALS AND STUDY DESIGN: The authors investigated the transmission dynamics of syphilis against a template based on the natural history of infection in individual patients with the aim of (1) identifying gaps in our understanding of the biology of infection, and (2) providing insights of relevance to the design of control policies. Analyses reveal that Treponema pallidum has a moderate to high probability of transmission during contact between susceptible and infectious sexual partners. This, combined with questions over the existence of any immunity to reinfection, helps to ensure the long-term persistence of syphilis within "core" activity groups. Patterns of treatment in North America are shown to have significantly altered the relative frequency of individuals in the different stages of disease. The analyses emphasize the benefits to be gained from treating infected people early in the primary stage of infection to reduce the effective period during which infected people can transmit to others. This form of treatment is beneficial for both the individual and the community. Treatment has greatly altered the incidence of different disease stages, but the full implications of treatment depend on whether immunity is present.
... Syphilis is a bacterial STI that is still widespread in resource-constrained countries and resurgent in high-income countries in specific risk groups [8]. After infection, the disease progresses through an incubation period lasting on average 3-4 weeks but with large fluctuations (10-90 days) [43]. It is then followed by two infective stages -primary and secondary syphilis. ...
... Within the variation of incubation duration reported in syphilis infected individuals [43], we find errors in elimination predictions ranging from −5% to 40% (Fig. 3d,e), if the model neglects incubation. The simple addition of one timescale in a non-infectious compartment induces an interplay with the timescales of the contacts and of the other disease stages, either boosting or hampering the conditions for syphilis spread. ...
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COVID-19 highlighted how modeling is an integral part of pandemic response. But it also exposed fundamental methodological challenges. As high-resolution data on disease progression, epidemic surveillance, and host behavior are now available, can models turn them into accurate epidemic estimates and reliable public health recommendations? Take the epidemic threshold, which estimates the potential for an infection to spread in a host population, quantifying epidemic risk throughout epidemic emergence, mitigation, and control. While models increasingly integrated realistic host contacts, no parallel development occurred with matching detail in disease progression and interventions. This narrowed the use of the epidemic threshold to oversimplified disease and control descriptions. Here, we introduce the epidemic graph diagrams (EGDs), novel representations to compute the epidemic threshold directly from arbitrarily complex data on contacts, disease and control efforts. We define a grammar of diagram operations to decompose, compare, simplify models, extracting new theoretical understanding and improving computational efficiency. We test EGDs on two public health challenges, influenza and sexuallytransmitted infections, to (i) explain the emergence of resistant influenza variants in the 2007-2008 season, and (ii) demonstrate that neglecting non-infectious prodromic stages biases the predicted epidemic risk, compromising control. EGDs are however general, and increase the performance of mathematical modeling to respond to present and future public health challenges.
... Therefore, we use the average of the recruitment rate and natural death rate per year from 2000 to 2019, i.e. = 4039262 and μ = 0.013 with units person/year and year −1 respectively (see Table 3). According to Garnett et al. (1997), the mean durations for primary and secondary syphilis are 46 and 108 days, respectively. Hence, we set the progression rates ρ 1 = 365/46 and ρ 2 = 365/108 with unit year −1 . ...
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Syphilis and HIV infections form a dangerous combination. In this paper, we propose an epidemic model of HIV-syphilis coinfection. The model always has a unique disease-free equilibrium, which is stable when both reproduction numbers of syphilis and HIV are less than 1. If the reproduction number of syphilis (HIV) is greater than 1, there exists a unique boundary equilibrium of syphilis (HIV), which is locally stable if the invasion number of HIV (syphilis) is less than 1. Coexistence equilibrium exists and is stable when all reproduction numbers and invasion numbers are greater than 1. Using data of syphilis cases and HIV cases from the US, we estimated that both reproduction numbers for syphilis and HIV are slightly greater than 1, and the boundary equilibrium of syphilis is stable. In addition, we observed competition between the two diseases. Treatment for primary syphilis is more important in mitigating the transmission of syphilis. However, it might lead to increase of HIV cases. The results derived here could be adapted to other multi-disease scenarios in other regions.
... These models have been constructed in large numbers to analyze the mechanics of the propagation of syphilis infection. In [19,20], the authors structured the propagation of the infection with the effect of treatment. Various categories were created throughout the population based on factors including age, sexual intercourse, and gender [21], but the latter stages of syphilis were integrated. ...
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One of the most harmful and widespread sexually transmitted diseases is syphilis. This infection is caused by the Treponema Palladum bacterium that spreads through sexual intercourse and is projected to affect $12$ million people annually worldwide. In order to thoroughly examine the complex and all-encompassing dynamics of syphilis infection. In this article, we constructed the dynamics of syphilis using the fractional derivative of the Atangana-Baleanu for more accurate outcomes. The basic theory of non-integer derivative is illustrated for the examination of the recommended model. We determined the steady-states of the system and calculated the $\mathcal{R}_{0}$ for the intended fractional model with the help of the next-generation method. The infection-free steady-state of the system is locally stable if $\mathcal{R}_{0} < 1$ through jacobian matrix method. The existence and uniqueness of the fractional order system are investigate by applying the fixed-point theory. The iterative solution of our model with fractional order was then carried out by utilising a newly generated numerical approach. Finally, numerical results are computed for various values of the factor $\Phi$ and other parameters of the system. The solution pathways and chaotic phenomena of the system are highlighted. Our findings show that fractional order derivatives provide more precise and realistic information regarding the dynamics of syphilis infection.
... The incidence of syphilis has been increasing steadily in recent years (1,2). It is believed that the agent of syphilis, Treponema pallidum (TP), invades the human skin or mucosa, then spreads to our body, and forms a long-term persistent chronic infection (3). Based on the time of infection, syphilis was divided into two stages, early and late stages. ...
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Introduction Syphilitic balanitis of Follmann (SBF) is a rare condition of primary syphilis which is characterized by any kind of balanitis with or without chancre on the penis combined with the presence of swollen inguinal lymph nodes confirmed by the finding of Treponema pallidum in the lesions or by the positive serological syphilitic testing. Timely identification of the SBF is very important in properly treating the disease stopping the spread of syphilis. Case presentation A 42year-old heterosexual male patient came to our clinic and complained of a painless, hard erythema nodule with a whitish scale in his coronal sulcus of the penis for about a week. The dermatologic examination revealed an infiltrative, hard erythematous lesion surrounding the coronal sulcus of the patient’s penis, with mild erosion and a small amount of exudation. There was a whitish pseudomembrane-like covering on the surface of the erythematous lesion in the coronal sulcus, which is mimicked as candidal balanitis. The result of the fungus microscopic examination was negative, while the laboratory findings showed positive results in serologic syphilitic testing. The patient was diagnosed with primary syphilis and intramuscularly treated with a dose of benzylpenicillin of 2.4 million units. The patient’s skin lesions disappeared completely 60 days after penicillin treatment. Conclusion To our knowledge, this is the first SBF case reported in China. Syphilitic balanitis of Follmann may have variable clinical appearances. We emphasize that when balanitis with risky sexual activities or with sexually transmitted diseases, the diagnosis of SBF should be kept in mind.
... These stages can be asymptomatic. Patients who remain untreated during early syphilitic states go on to develop latent syphilis [1,2]. The clinical manifestations of tertiary syphilis vary greatly; however, the most common clinical manifestations include aortitis, gummatous syphilis, and neurosyphilis. ...
Article
Ocular syphilis has a wide range of presentations; however, the most common findings are ophthalmalgia, blurry vision, and erythematous conjunctiva. This report presents a case of ocular syphilis in a human immunodeficiency virus-positive patient with an allergy to penicillin. On presentation, the patient was diagnosed using a fluorescent treponemal antibody absorption test, in addition to rapid plasma reagin. In this case, the patient received alternative treatment with doxycycline prior to penicillin desensitization, with marked improvement of his symptoms.
... The partial immunity to syphilis can be responsible for time oscillation. Besides, the transmission rate of syphilis is higher than that of gonorrhea (22,23) . So, any subjacente periodicity would be more pronounced. ...
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Introduction: Syphilis is a systemic, chronic, curable, and unique bacterial infection in humans, transmitted sexually, mainly. When untreated, it evolves to stages that range in severity and can affect different body organs and systems. Objective: To delineate whether or not there are significant changes in the demand and positivity of the nontreponemal test, after Carnival or at other times in the analyzed years, from January 2014 to December 2019, in a laboratory in the private health network of Niteroi. Methods: A retrospective, quantitative and descriptive study was carried out aiming at defining the profiles of the population that seeks a particular laboratory to undergo the nontreponemal test from 2014 to 2019. Data collection was carried out through documental analysis of the results, with an authorization from the laboratory, preserving the confidentiality of patients. The seasonal decomposition, which is a monthly time series, was performed to assess the trend and exponential trend using the additive model. Results: A total of 34,817 tests were performed, with 1,637 positivity of the nontreponemal test results in the analyzed years, using the SPSS program. There was an increase in the number of exams in 2019 (6,488), maintaining the distribution during this year. Conclusion: Both the demand and the positivity of the nontreponemal tests have increased significantly over the years, finding no seasonality in relation to reactive of the nontreponemal tests.
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Syphilis outbreak is a global threat as it leads to increase in the number of persons be infected with human immunodeficiency virus (HIV). In this article, mathematical modelling frame work governed by a system of differential equations that integrated both HIV and Syphilis outbreaks in Nigeria was proposed. The stability analysis of the HIV and Syphilis sub-models were investigated and the basic reproduction number was obtained using Next Generation Matrix method. It is observed that the disease free equilibrium is locally and globally stable when 0 < 1 and unstable when 0 > 1. Numerical simulations of the model equations and sensitivity analysis were carried out to illustrate the impact of dynamics in the disease transmission and the most sensitive parameters and useful recommendations were made.
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Pathogen traits can vary greatly and heavily impact the ability of a pathogen to persist in a population. Although this variation is fundamental to disease ecology, little is known about the evolutionary pressures that drive these differences, particularly where they interact with host behaviour. We hypothesized that host behaviours relevant to different transmission routes give rise to differences in contact network structure, constraining the space over which pathogen traits can evolve to maximize fitness. Our analysis of 232 contact networks across mammals, birds, reptiles, amphibians, arthropods, fish and molluscs found that contact network topology varies by contact type, most notably in networks that are representative of fluid-exchange transmission. Using infectious disease model simulations, we showed that these differences in network structure suggest pathogens transmitted through fluid-exchange contact types will need traits associated with high transmissibility to successfully proliferate, compared to pathogens that transmit through other types of contact. These findings were supported through a review of known traits of pathogens that transmit in humans. Our work demonstrates that contact network structure may drive the evolution of compensatory pathogen traits according to transmission strategy, providing essential context for understanding pathogen evolution and ecology.
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Pathogen traits can vary greatly and impact the ability of a pathogen to persist in a population. Although this variation is fundamental to disease ecology, little is known about the evolutionary pressures that drive these differences, particularly where they interact with host behavior. We hypothesized that host behaviors relevant to different transmission routes give rise to differences in contact network structure, constraining the space over which pathogen traits can evolve to maximize fitness. Our analysis of 232 contact networks across mammals, birds, reptiles, amphibians, arthropods, fish and mollusks found that contact network topology varies by contact events, most notably in networks that are representative of fluid-exchange transmission. Using infectious disease model simulations, we showed that these differences in network structure suggest pathogens transmitted through fluid-exchange contact events will need traits associated with high transmissibility in order to successfully proliferate, compared to pathogens that transmit through other types of contact. These findings were supported through a review of known traits of pathogens that transmit in humans. Our work demonstrates that contact network structure may drive the evolution of compensatory pathogen traits according to transmission strategy, providing essential context for understanding pathogen evolution and ecology.
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The prevalence and transmission of syphilis was studied in a semirural community in south eastern Gabon. The overall prevalence was 8% (99/1251) and there was no difference in age adjusted prevalence between men and women. The transmission of syphilis between sexual partners occurred in 18.1% (8/44).
Article
T-cell mediated delayed-type hypersensitivity (DTH) is the predominant immune mechanism for clearing tissues of infecting organisms in the primary lesion of syphilis. Here, Stewart Sell and Pei-Ling Hsu propose a strategy for vaccination against syphilis in which selective induction of DTH may be accomplished by using BCG vectored vaccines containing selected DNA sequences for T. pallidum antigens.
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In a cooperative clinical study, several intramuscular treatment schedules were tested for their effectiveness in preventing the development of syphilis in persons who had been exposed to infectious syphilis. The study population consisted of 788 clinically and serologically negative contacts at five treatment centers. A part of the study group received a placebo similar in appearance to one of the drugs being tested and given in the same manner. No cases developed among contacts treated with 2,400,000 units of benzathine penicillin G given in one treatment at one or two intramuscular injection sites. Intramuscular injections of 600,000 units of aqueous procaine penicillin G or of benzathine penicillin G or an intramuscular tetracycline preparation given in a dosage of 500 mg. on 2 successive days gave unsatisfactory results. Of 182 patients given placebo, 16, or 9.2 percent (cumulative rate based on number observed for varying periods), developed syphilis during the 3-month followup period.