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ScienceWeek
EPIDEMIOLOGY: ON SYPHILIS EPIDEMICS
The following points are made by B. Grenfell and O. Bjørnstad (Nature 2005 433:366):
1) The Renaissance physician and scholar Girolamo Fracastoro (1478-1553) achieved lasting fame for his early observations on the contagion theory of the transmission of infectious disease[1]. In 1530, he also coined the name for syphilis --which was then spreading rapidly through Europe -- in an extended allegory written in Latin hexameter (epidemiologists were more culturally rounded in those days). In Fracastoro's poem, the god Apollo is angered by a shepherd, Syphilus, and afflicts him with the new disease. Recent work[2] has provided a more mundane explanation of the dynamic processes underlying the incidence of syphilis.
2) Whether fluctuations in epidemics are governed by external drivers (such as behavior or climate), or by intrinsic processes that arise from the dynamic feedback between host and pathogen populations, has been debated since the early 1900s. This controversy parallels long-standing ecological arguments about the relative role of extrinsic (environmental) forces and intrinsic nonlinear dynamics in driving population fluctuations[3]. Arguably, ecologists are more familiar than epidemiologists with the potential of nonlinear dynamics to drive cycles. This is ironic, because many infectious diseases have excellent historical records of incidence and a simple natural history -- an ideal combination for exploring the underpinnings of dynamic fluctuations[4,5].
3) Comparative approaches, where differences in the dynamics of various infections can be related to biological differences in the underlying host-pathogen interactions, are particularly powerful in studying this problem. Grassly et al[2] used this approach to explore the dynamics of syphilis and gonorrhea. They base their analysis on disease notification statistics from the United States, where these two sexually transmitted diseases are endemic. The authors use time series of annual disease reports for 68 US cities to demonstrate marked 8-11-year cycles in syphilis incidence from the 1960s to the 1980s. These cycles had previously been attributed to changes in factors extrinsic to the host-pathogen interaction, particularly to changes in human sexual behavior. If this were the case, however, there should be correlated fluctuations in gonorrhea because of its similar transmission route and infectious period. Grassly et al[2] demonstrate that there is no such correlation: gonorrhea shows slow trends rather than cycles during the same period.
4) Grassly et al[2] use mathematical models to reveal that the distinct behaviors of syphilis and gonorrhea arise from their different interactions with the human immune system. Thus, the simplest explanation for the periodicity in syphilis incidence is that it results from nonlinear interactions that are fundamental to the host-pathogen transmission process. Syphilis stimulates significant -- albeit imperfect -- immunity following recovery from infection. Consequently, as Grassly et al[2] demonstrate, the dynamics of syphilis infection have many features of the well-known "susceptible-infected-recovered" (SIR) model for microparasitic infections[4,5]. In SIR dynamics, oscillations in disease incidence can be driven by prolonged immunity following infection (combined with a relatively short infection period[4]). Cycles occur because major epidemics extinguish themselves by exhausting their supply of susceptible individuals; the numbers of individuals in at-risk groups then build up slowly, eventually providing enough scope for the next major outbreak.
References (abridged):
1. Gould, S. J. Nat. Hist. 109, 38-47 (2000)
2. Grassly, N. C., Fraser, C. & Garnett, G. P. Nature 433, 417-421 (2005)
3. Bjørnstad, O. N. & Grenfell, B. T. Science 293, 638-643 (2001)
4. Anderson, R. M. & May, R. M. Infectious Diseases of Humans: Dynamics and Control (Oxford Univ. Press, 1992)
5. Grenfell, B. T., Bjørnstad, O. N. & Kappey, J. Nature 414, 716-723 (2001)
Nature http://www.nature.com/nature
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MEDICAL BIOLOGY: ON THE RESURGENCE OF SYPHILIS
The following points are made by M.R. Golden et al (J. Am. Med. Assoc. 2003 290:1510):
1) In 1937 US Surgeon General Thomas Parran estimated that 10% of Americans would be infected with syphilis during their lives.(1) Rates of primary and secondary syphilis plummeted with the institution of public health control measures and the advent of penicillin, reaching a nadir in 2000. Since then, rates have continued to decline among women and infants, although overall rates again have begun to climb.(2)
2) The dominant epidemiological features of syphilis in the US today include varying incidence rates by geography, race and sexual orientation, and an association with human immunodeficiency virus (HIV). Syphilis rates among heterosexuals in the United States are highest in the south, where 16 states reported 53% of all US cases in 2001, including 64% of all cases in women.(2) Syphilis disproportionately affects blacks. In 2001, reported US rates of primary and secondary syphilis were 42 times higher among black women than among white women.(2) Racial disparities likely reflect not only bias in syphilis reporting and differential access to medical care but also racial segregation in sexual activity, and other differences in sexual networks between ethnic groups.(3)
3) Since 1997, increases in syphilis rates among men who have sex with men have been documented in Seattle, Chicago, southern California, San Francisco, New York, Miami, Boston, and several European and Canadian cities.(4) Rates of other sexually transmitted diseases (STDs) also have risen among men who have sex with men, reflecting a general increase in unsafe sexual behavior with the availability of potent antiretroviral therapy for HIV.(5) Although national reporting does not capture information about sexual orientation, in 2001 the estimated rate per 100,000 of primary and secondary syphilis in King County, Washington was 141 among men who have sex with men, 683 among men who have sex with men infected with HIV, and less than 1 among heterosexuals (H.H. Handsfield, oral communication, April 2003).
4) Cities in the United States have reported that 20% to 73% of men who have sex with men with syphilis are HIV-infected vs a median HIV seroprevalence of 12.5% among women with syphilis in studies published between 1995 and 1998. Epidemiologic studies and studies documenting increased HIV shedding associated with genital ulcers strongly suggest that syphilis increases both the susceptibility of infected persons to HIV acquisition and the likelihood that dually infected persons transmit HIV to their sex partners.
5) Syphilis passes through a series of frequently overlapping stages. Treponema pallidum, a spirochete, causes syphilis and is spread through contact with infectious lesions or body fluids. Studies from the preantibiotic era typically found that 50% to 75% of exposed sex partners of persons with primary or secondary syphilis were infected, and that among contacts without clinical or serological evidence of infection on initial evaluation, approximately 30% developed syphilis in the absence of treatment. Patients typically develop a skin lesion (chancre) at the site of inoculation approximately 21 days after exposure. Chancres frequently go unnoticed, particularly among women and men who have sex with men who may not be able to see vaginal or anal lesions.
References (abridged):
1. Parran T. Shadow on the Land. New York, NY: Reynal & Hitchcock; 1937.
2. Centers for Disease Control and Prevention, National Center for HIV, STD and TB Prevention, Division of Sexually Transmitted Diseases. Sexually Transmitted Diseases Surveillance 2001. Atlanta, Ga: CDC; September, 2002
3. Laumann EO, Youm Y. Racial/ethnic group differences in the prevalence of sexually transmitted diseases in the United States: a network explanation. Sex Transm Dis. 1999;26:250-261
4. Ciesielski CA. Sexually transmitted diseases in men who have sex with men: an epidemiologic review. Curr Infect Dis Rep. 2003;5:145-152
5. Katz MH, Schwarcz SK, Kellogg TA, et al. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men: San Francisco. Am J Public Health. 2002;92:388-394
J. Am. Med. Assoc. http://www.jama.com
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COMPLETE GENOME SEQUENCE OF SYPHILIS SPIROCHETE
Notes by ScienceWeek:
Syphilis is a contagious systemic disease caused by the *spirochete microbe Treponema pallidum, the disease characterized by sequential clinical stages and by years of latency without symptoms. It can affect any tissue or vascular organ of the body and can be passed from mother to fetus. One hundred years ago, syphilis was a scourge of the industrialized nations. Since the introduction of penicillin and the organization of a national control program in the 1940s, the prevalence of syphilis has been markedly reduced, and the prevalence currently ranges from approximately 20 cases per 100,000 in 1990 to 3.2 cases per 100,000 in 1997, with maxima and minima following what appears to be 7 to 10 year cycles, and with more than 50 percent of the cases in the US occurring in only 31 counties.
The following points are made by Fraser et al (Science 1998 281:375):
1) The authors report they have determined the complete genome sequence of T. pallidum, the microbe's genome comprising 1,138,006 *base pairs containing 1041 predicted coding sequences (*open reading frames). Systems for DNA replication, *transcription, *translation, and repair are intact, but *catabolic and biosynthetic activities are minimized. Potential virulence factors include a family of 12 possible membrane proteins and several assumed hemolysins.
2) Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi, the agent of Lyme disease, reveals unique and common genes, and substantiates the considerable diversity observed among pathogenic spirochetes.
3) The authors point out that T. pallidum has been a difficult organism to study experimentally because of its absolute dependence on a mammalian host for sustained growth and viability, and that knowledge of the genomic sequence of the organism may provide a foundation for the development of a culture medium and open the possibility of future genetic studies.
Science http://www.sciencemag.org
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Notes by ScienceWeek:
spirochete: In general, this refers to various bacteria species that assume a spiral form and range in size from a few microns to 500 microns in length. T. pallidum, the agent of syphilis, is 3 to 8 microns in length, with acute regular or irregular spirals.
base pairs: The term "base pair" refers to the bases (nucleotides) always found chemically bonded together in the DNA double helix (adenine, for example, always bonds with thymine, and guanine with cytosine).
open reading frames: The term "reading frame" refers to a specific permutation of nucleotide triplets in DNA as "framed" by a preceding start triplet (start codon), and an open reading frame is any DNA sequence of triplets that potentially encodes a protein.
transcription: *Transcription is the process by which genetic information in DNA is converted into RNA.
translation: Translation is protein synthesis, the process during which polypeptides are synthesized on ribosomes in accordance with RNA code.
catabolic: This refers to catabolism, the enzyme-mediated breakdown of complex organic substances into simple substances, with conversion of the energy stored in chemical bonds to the bond energy of ATP (adenosine triphosphate). A companion term is "anabolism", which refers to the opposite process -- the enzyme synthesis of complex molecules from simple molecules. The term "metabolism" refers to the totality of physical and chemical processes occurring in a living organism, and comprises both anabolism and catabolism.
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