Syphilis Research Paper
Syphilis Research Paper
Syphilis is a sexually transmitted disease that spreads from a small sore. This disease is caused by a bacterium scientifically named treponema pallidum. If the disease is not treated in its initial stages then it could cause fatalities in the future. The disease can be protected by the use of condoms. Otherwise, the symptoms include a non-itchy sore that appears on the skin. The later stages are very fatal and could cause death.
The bacteria that cause syphilis can affect the penis, the vagina or the urethra and anus. There are three stages of syphilis. These stages include the primary, secondary and the final stage. The first stage is depicted by a painless sore that appears in an area of the body. The syphilis symptoms then come and go for close to one or two years. If treatment is not availed then the disease could cause death to the patient. Syphilis Research Paper.
Although not entirely transmitted through sexual activity, the infection can at times be passed on from one person to another through open wounds or close skin contact especially when rashes are present. The bacterium that causes the sexually transmitted infection is treponema pallidum and affects both genders in different ways.The incubation period for the disease ranges from three weeks to three months which is experienced in 3 states that is characterized by different symptoms.
Stage 1 (primary level stage)
In the first stage which is usually between 4 -12 weeks, the patient may experience painless sores which usually occur around the genital area or the mouth. These sores may go unnoticed or may be mistaken for just a simple rash and they heal completely within 4 weeks. They are hardly noticeable and most individuals will ignore the call to see a doctor or a physician.
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Stage 2 (secondary stage)
During this stage, which can take up to a year to develop, the patient experiences a sore throat and skin rashes that develop at the soles of the feet or the palms of the hand. This stage is the most contagious and can be mistaken for a skin condition. Other non-specific symptoms that may be experienced in this stage are hair loss, pain in the joints and flu like illness. Syphilis Research Paper. These symptoms disappear after a while after which the patient undergoes a hidden phase with no symptoms where the infection goes undetected unless tested by a medical specialist CITATION Ada06 \l 1033 (Winters). This can last for years after which the patient progresses to the third stage. The third stage is the tertiary stage and is the most dangerous of all.
Stage 3 (tertiary stage)
At this stage, which is regarded as the full blown infection patients may experience organ complications which affect mainly the brain, heart and may cause blindness. This stage occurs about 5-10 years after the initial infection although it cannot be passed from one person to another it is still treatable if proper medical attention is sought. The danger of this stage is that once most of the organs have been damaged, the ability for repair reduces drastically.
Pregnant mothers who are also infected with syphilis risk infecting their unborn babies. When unborn babies are infected, the condition is known as congenital syphilis which includes symptoms like skin rashes, eye problems, runny nose which can result to deafness or eye problems to the baby.
Syphilis is easily treatable through use of penicillin at all stages. Although it can go undetected, patients who experience such symptoms are encouraged to go for a blood or swab test that can ascertain the presence of the bacterial infection. Otherwise, waiting for too long might only lead to severe problems that might be unsolved or even death.
For an individual to identify whether he or she has syphilis a doctor should be sought after in order to perform tests. These tests can be done at the laboratory to check on the bacterium that causes the disease. It is advisable that if an individual is not sure of an appearing sore then he should check on a physician. Partners can be infected by the disease minus their knowledge but upon detecting that one is infected the best way to treat the disease is by administering antibiotics. Even the other partner should be informed so that the two receive treatment in advance.
It is also important to realize the fact that at the later stages of syphilis, the damage that was initially caused cannot be undone at all. Thus it is important to visit the clinic for regular medication. This will save a lot of damage that can be caused as a result of ignorance. Syphilis can be spread from pregnant woman to her unborn child or the fetus. This could lead to a problem in giving birth in what is termed as still birth. There might arise complications as a result of this disease. Therefore, early treatment should be sought to avoid futuristic problems. Syphilis Research Paper.
Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochetes and often imitate those of other diseases. The spirochete has a long latent period during which patients have no signs or symptoms, but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries. Syphilis also causes several hundred thousand stillbirths and neonatal deaths every year in developing nations.Syphilis Research Paper. Although several low-income countries have achieved WHO targets for the elimination of congenital syphilis, an alarming increase of syphilis in HIV-infected MSM serves as a strong reminder of the tenacity of T. pallidum as a pathogen. Strong advocacy and community involvement is needed to ensure that syphilis is given high priority on the global health agenda. More investment in research is needed on the interaction between HIV and syphilis in MSM, as well as into improved diagnostics, a better test of cure, intensified public health measures and, ultimately, a vaccine.
Syphilis is a sexually and vertically transmitted infection (STI) caused by the spirochaete Treponema pallidum subspecies pallidum (order Spirochaetales) (Fig. 1). Three other organisms within this genus are causes of nonvenereal or endemic treponematoses. T. pallidum subspecies pertenue is the causative agent of yaws, T. pallidum subspecies endemicum causes endemic (non-venereal) syphilis and T. carateumcauses pinta. These pathogens are morphologically and antigenically indistinguishable. They can, however, be differentiated by their age of acquisition, principal mode of transmission, clinical manifestations, capacity for invasion of the central nervous system and placenta, and genomic sequences, although the accuracy of these differences remains a subject of debate1. Analyses based on the mutation rates of genomic sequences suggest that the causative agents of yaws and venereal syphilis diverged several thousand years ago from a common progenitor originating in Africa2. These estimates argue against the so-called Columbian hypothesis — the notion that shipmates of Christopher Columbus imported a newly evolved spirochete causing venereal syphilis from the New World into Western Europe in the late 15th century3.
A | Like all spirochetes, T. pallidum consists of a protoplasmic cylinder and cytoplasmic membrane bounded by a thin peptidoglycan sacculus and outer membrane239,240. Usually described as spiral-shaped, T. pallidum is actually a thin planar wave similar to Borrelia burgdorferi, the agent of Lyme borreliosis239.Syphilis Research Paper. The bacterium replicates slowly and poorly tolerates desiccation, elevated temperatures and high oxygen tensions55. B | Periplasmic flagellar filaments, a defining morphological feature of spirochetes, originate from nanomotors situated at each pole and wind around the cylinder atop the peptidoglycan, overlapping at mid-cell. Force exerted by the rigid filaments against the elastic peptidoglycan deforms the sacculus to create the flat wave morphology of the spirochete100. Panel B used with permission from Ref.239 C | Ultra-thin section of T. pallidum showing the outer and cytoplasmic membranes and flagellar filaments (endoflagella) within the periplasmic space9. D | Surface rendering of a flagellar motor based on cryoelectron tomograms. Panel D used permission from Ref.240. E | Darkfield micrograph showing the flat-wave morphology of Tpallidum. The arrow and arrowhead indicate segments that are oriented 90° from each other. The different appearances of the helical wave at 90° to the viewer can be explained only by a flat wave morphology; a corkscrew would appear the same from any angle. Panel E used permission from Ref 239.
T. pallidum is an obligate human pathogen renowned for its invasiveness and immunoevasiveness4–7; clinical manifestations result from the local inflammatory response elicited by spirochetes replicating within tissues8–10. Infected individuals typically follow a disease course divided into primary, secondary, latent and tertiary stages over a period of ≥10 years. Different guidelines define early latency as starting 1–2 years after exposure. Typically, ‘early syphilis’ refers to infections that can be transmitted sexually (including primary, secondary and early latent infections) and is synonymous with active (infectious) syphilis; the WHO defines ‘early syphilis’ as infection of <2 years duration11, whereas the guidelines from the United States12 and Europe13 define it as infection <1 year in duration. These differences in definition can affect interpretation of results and in therapeutic regimens used in some circumstances.
Owing to its varied and oSyphilis Research Paper.ften subtle manifestations that can mimic other infections, syphilis has earned the names of the Great Imitator or Great Mimicker14. Patients with primary syphilis present with a single ulcer (chancre) or multiple lesions on the genitals or other body sites involved in sexual contact and regional lymphadenopathy ~3 weeks post-infection; these are typically painless and resolve spontaneously. Resolution of primary lesions is followed 6–8 weeks later by secondary manifestations, which can include fever, headache and a maculopapular rash on the flank, shoulders, arm, chest or back and that often involves the palms of the hands and soles of the feet. As signs and symptoms subside, patients enter a latent phase, which can last many years. A patient in the first 1–2 years of latency are still considered infectious owing to a 25% risk of secondary syphilis-like relapses15. Historical literature suggests that 15–40% of untreated individuals will develop tertiary syphilis, which can manifest as destructive cardiac or neurological conditions, severe skin or visceral lesions (gummas) or bony involvement9.Syphilis Research Paper. More-recent data suggest tertiary syphilis may be less common today, perhaps owing to wide use of antibiotics. Numerous case reports and small series suggest that HIV infection predisposes to neuro-ophthalmological complications in those with syphilis16. Importantly, neurosyphilis is typically described as a late manifestation but can occur in early syphilis. Indeed, T. pallidum can be frequently identified in the cerebral spinal fluid (CSF) of patients with early disease9,15,17. However, the majority of patients with early syphilis who have CSF abnormalities do not demonstrate central nervous system symptoms and do not require therapy for neurosyphilis12. Symptomatic manifestations of neurosyphilis include chronic meningitis, meningovascular stroke-like syndromes and manifestations common in the neurological forms of tertiary syphilis (namely, tabes dorsalis and general paresis, a progressive dementia mimicking a variety of psychotic syndromes)9.
Sexual transmission of syphilis occurs during the first 1–2 years after exposure (that is, during primary, secondary and early latent stages of infection) 9. The risk of mother-to-child transmission (MTCT) is highest in primary and secondary stages, followed by early latent syphilis. However, transmission risk continues during the first 4 years after exposure, after which vertical transmission risk declines over time18. The rate of fetal infection depends on stage of maternal infection, with approximately 30% of pregnancies resulting in fetal death in utero, stillbirth (late second and third trimester fetal death) or death shortly after delivery19–21. Infants born to infected mothers are often preterm, of low birth weight or with clinical signs that mimic neonatal sepsis (that is, poor feeding, lethargy, rash, jaundice, hepatosplenomegaly and anaemia).
Given that T. pallidum has a relatively long generation time of 30–33 hours22, long-acting penicillin preparations such as benzathine penicillin G is the preferred therapy for most patients with syphilis. Since the 1940s (when penicillin became widely available), syphilis prevalence continued decline in regions able to appropriately test and treat the infection. However, syphilis outbreaks continue to occur throughout the world. In particular, with declining AIDS-related mortality related to effective HIV treatment over the past two decades, syphilis has re-emerged in urban settings among men who have sex with men (MSM). High-income and middle-income countries have observed rises in syphilis case rates as well as increased case rates of neurosyphilis (such as ocular syphilis) and, in some countries, congenital syphilis. In low income countries where syphilis prevalence remains high, MTCT of syphilis continues to be the most common cause of STI-related mortality outside of HIV23,24, with perinatal deaths owing to untreated syphilis exceeding those of HIV or malaria25. Syphilis is now the second leading cause of preventable stillbirths worldwide, following malaria25. Syphilis Research Paper.
Syphilis should be an ideal disease for elimination as it has no known animal reservoir, can usually be diagnosed with simple inexpensive tests and can be cured9,16. Nevertheless, syphilis remains a continuing public health challenge globally26. In this Primer, we describe recent discoveries that have improved our understanding of the biological and genetic structure of the pathogen, novel diagnostic tests and testing approaches that can improve disease detection, as well as current, evidence-based management recommendations. We also draw attention to the call for global elimination of MTCT of syphilis and HIV and recent success in elimination in in low and middle income countries (LMICs), particularly through fundamental public health strategies such as ensuring quality antenatal care that includes testing for syphilis early in pregnancy and providing prompt treatment of women and their partners. We also report on the rising numbers of syphilis cases in MSM, ongoing work supporting improved interventions against syphilis in marginalized populations and, ultimately, development of an effective vaccine.
Epidemiology
According to the most recent estimation of the WHO, approximately 17.7 million individuals 15–49 years of age globally had syphilis in 2012, with an estimated 5.6 million new cases every year27 (Fig. 2). The estimated prevalence and incidence of syphilis varied substantially by region or country, with the highest prevalence in Africa and >60% of new cases occurring in LMICs27. The greatest burden of maternal syphilis occurs in Africa, representing >60% of the global estimate23,24.
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The WHO estimates of incident cases of syphilis by region in 2012 are shown for the different geographical regions. Data from Ref.27
Prevalence and incidence
In LMICs, heterosexual spread of syphilis has declined in the general population but remains problematic in some high-risk sub-populations, such as female sex workers (FSWs) and their male clients. A recent study of FSWs in Johannesburg, South Africa, showed that 21% of participating women had antibodies that suggested past or current infection and 3% had active (infectious) infection28. Another study of FSWs in 14 zones in Sudan showed high seroprevalence (median 4.1%), with the highest value of 8.9% in the eastern zone of the country29. A large study of >1,000 FSWs in Kampala, Uganda, showed 21% were seropositive for syphilis and 10% had active infection30. Studies in emerging economies, such as China, indicate that syphilis is increasing among ‘mobile men with money’31.Syphilis Research Paper. Although syphilis case rates are low in the general population in China, syphilis prevalence is ~5% among FSWs and 3% among their male clients31,32. Risk of infection varies among FSWs working in different venues, with the highest prevalence (~10%) among street-based FSWs and lower prevalence (~2%) among venue-based FSWs33.
By contrast, higher-income countries have had declining syphilis prevalence among heterosexual men and women. However, a resurgence of syphilis that disproportionately affects MSM has been noted. Syphilis is associated with high-risk sexual behaviours and substantially increased HIV transmission and acquisition. Indeed, the numbers and rates of reported cases of syphilis among MSM in the United States and Western Europe have been increasing since 1998 (Ref.34). In 2015, the case rates for primary and secondary syphilis among MSM (309 per 100,000) in the United States were 221-times the rate for women (1.4 per 100,000) and 106 times the rate for heterosexual men (2.9 per 100,000)35. In Canada, compared with reported cases in the general male population, the incidence of syphilis was >300-times greater among HIV-positive MSM36. Syphilis infection has been associated with certain behavioural and other factors, including incarceration; multiple or anonymous sex partners; sexual activity connected with illicit drug use; seeking sex partners through the internet and other high-risk sexual network dynamics37–41. Risk factors for syphilis are frequently overlapping40. Reports of unusual presentations and rapid progression of syphilis in patients with concurrent HIV infection has led to the hypothesis that infection with or treatment for HIV alters the natural history of syphilis42. Syphilis Research Paper.
MTCT
Adverse birth outcomes caused by fetal exposure to syphilis are preventable if women are screened for syphilis and treated before the end of the second trimester of pregnancy21. However, MTCT of syphilis continued to cause such perinatal and infant mortality that, in 2007, the WHO and partners launched a global initiative to eliminate it as a public health problem43–45. At the time of the campaign launch, an estimated 1.4 million pregnant women had active syphilis infections, of whom 80% had attended at least one antenatal visit — suggesting missed opportunities for testing and treatment23. At that time, untreated maternal syphilis infection was estimated to have resulted in >500,000 adverse pregnancy outcomes, including more than 300,000 perinatal deaths (stillbirths and early neonatal deaths).
Syphilis testing and treatment during pregnancy is highly effective and was included in the Lives Saved Tools of effective maternal–child health interventions46. Furthermore, studies have shown that prenatal syphilis screening, treatment support testing and treatment during pregnancy are highly cost-effective in most countries regardless of prevalence or availability of resources, and can even be cost-saving in LMICs with syphilis prevalence ≥3% in pregnant women47–50. In China, where syphilis and HIV prevalence in pregnant women is low but rising, integration of prenatal syphilis and HIV screening was found to be highly cost-effective51.
Since 2007, an increasing number of countries have implemented regional and national initiatives to prevent MTCT of syphilis52, improving guidance documents, using point-of-care (POC) tests as a means of improving access to testing and treatment and integrating behavioural and medical interventions into HIV prevention and control programmes53.Syphilis Research Paper. By 2012, these efforts had contributed to a reduction in global adverse pregnancy outcomes due to MTCT of syphilis to 350,000, including 210,000 perinatal deaths, and decreased the rates of maternal and congenital syphilis decreased by 38% and 39%, respectively23,24. In 2015, Cuba became the first country to be validated for having achieved elimination of MTCT of HIV and syphilis54. Subsequently, Thailand, Belarus and four United Kingdom Overseas Territories (Bermuda, the Cayman Islands, Montserrat and Antigua) was validated for elimination of MTCT of HIV and syphilis, Moldova was validated for elimination of MTCT of syphilis, and Armenia was validated for elimination of MTCT of HIV. However, these gains were mostly in Asia and the Americas — maternal prevalence in Africa has remained largely unchanged23,24. Syphilis Research Paper.
