Re-Emergence of Syphilis in Women of Reproductive Age and its Association with the Increase in Congenital Syphilis, The Case of Mexico During the Years 2010-2019

Re-Emergence of Syphilis in Women of Reproductive Age and its Association with the Increase in Congenital Syphilis, The Case of Mexico During the Years 2010-2019 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Re-Emergence of Syphilis in Women of Reproductive Age and its Association with the Increase in Congenital Syphilis, The Case of Mexico During the Years 2010-2019 Santa García-Cisneros, Antonia Herrera-Ortiz, Maria Olamendi-Portugal, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-607054/v2 This work is licensed under a CC BY 4.0 License Status: Under Review Version 2 posted 11 You are reading this latest preprint version Show more versions Abstract Background: Syphilis is a sexually transmitted infection that is re-emerging in different parts of the world. This infection can be transmitted during pregnancy causing neonatal syphilis. The objective of the study was to determine the trend of syphilis, congenital syphilis, and mortality from congenital syphilis among the Mexican population between the years 2010-2019. Methods. We formed databases about the incidence of syphilis, the incidence of congenital syphilis, cases of congenital syphilis, and deaths of congenital syphilis using information from the Morbidity and Mortality Yearbooks and the Bulletin of the Mexican Ministry of Health, considering age, sex, the states of Mexico, and year. The trend was analyzed using linear regression, the increase was estimated with 95% confidence intervals, and p<0.05 was considered statistically significant. Results. The incidence of syphilis increases on average 0.336 cases/100,000, being higher among women aged 15-19 years (0.693 cases). Congenital syphilis has grown, from 62 cases in the year 2010 to 372 cases in the year 2019; the cases of congenital syphilis have relation to the increase of syphilis among women aged 20-24 years. Fifty percent of the states of Mexico without cases of congenital syphilis in 2010, but only 10% in 2018. Between the years 2010 to 2017, 62 deaths from congenital syphilis were reported. Conclusion. Congenital syphilis is increasing in Mexico, as a consequence of the reemergence of syphilis among the population of reproductive age, it is necessary to attend to syphilis in various population groups. Infectious Diseases Syphilis Congenital Syphilis Sexually Transmitted Diseases Mexico Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subs pallidum . Syphilis had four stages, the primary stage begins with the chancre which appears on the glans, penis, labia majora, labia minora, the perineum, or extragenital regions (palate, anus, rectus, fingers, or tongue). 1 The secondary syphilis is characterized by the systemic bacterial spread, erythematous rashes appear on palms of hands, soles of feet, chest, and back. Later there is a latency phase, without any clinical manifestation, but the non-treponemal serological tests remain positive, this stage can last up to 20 years. The infection continues and the tertiary stage is developed, affecting cardiovascular, nervous, and musculoskeletal systems. 1 – 3 T. pallidum can traverse the placental barrier, causing congenital syphilis. About 50% of pregnant women infected with T. pallidum and not treated, transmit syphilis to their child before birth. Among people living with HIV the natural history of syphilis is altered, there are more cases with tertiary syphilis, and the cases are found in a shorter time, and the presence of syphilis increases the transmission of HIV. 4 , 5 . According to the World Health Organization (WHO) in 2016, the incidence of curable STIs in the world was estimated at 376.4 million new cases among people aged 15 to 49 years, of which 6.3 million correspond to syphilis, resulting in a worldwide incidence of 1.5 cases per 1000 inhabitants and 2.0 cases per 1000 inhabitants in America. 6 Furthermore, syphilis caused 200,000 stillbirths and deaths worldwide, making it one of the leading causes of newborn deaths. In the Americas region, an estimated 22,800 cases of mother-to-child transmission of syphilis were estimated, with a rate of 1.7 cases per 1,000 live births. 7 In Mexico, an increase in the incidence of syphilis was detected between 2003 and 2013, concentrating among men aged 20–24 years and 25–44 years. 8 The objective of this study was to determine the trend of syphilis and congenital syphilis in Mexico, between the years 2010 to 2019, through the information available in the General Directorate of Epidemiology of the Ministry of Health of Mexico. Methods We review the information about the incidence of syphilis, the incidence of congenital syphilis, and cases of congenital syphilis from the Morbidity Yearbooks of the General Directorate of Epidemiology of the Ministry of Health from the year 2010 to 2019. No administrative permissions were required to access the data, the information is freely accessible. Databases were formed with syphilis information and age, sex, year, and states of Mexico variables, without any variable that could identify the participants. A second database was formed, using the number of infant deaths, the year, and the state of Mexico, with information from the Morbidity and Mortality Yearbooks and the Bulletin of the Ministry of Health. The trend analysis of syphilis incidence among women, syphilis incidence among men, and congenital syphilis, from 2010 to 2019, evaluated the average change through linear regression, with 95% confidence intervals (95% CI). Subsequently, with the t-student test for slopes, the trends by age groups stratified by sex were evaluated, it was considered statistically significant p < 0.05. The number of cases of congenital syphilis was stratified into 0–2 cases, 3–10 cases, 11–20 cases and 21 or more cases, a comparison was made between the years 2010 and 2019 considering each state of the republic. Subsequently, the information on mortality from congenital syphilis was analyzed, with information on the year of the report and status. Finally, the correlation between trends in congenital syphilis cases and incidence of syphilis in women aged 15–19 years and 20–24 years was evaluated, as well as the correlation between incidence of congenital syphilis and incidence of syphilis among women aged 20–24 years. for each state of the republic, using the Spearman correlation test. The tests were statistically significant with p < 0.05, all analyzes were carried out with the statistical program Graph Pad 10.0 Results The highest incidence of syphilis in the general population was observed in 2019 with 6.09 cases per 100,000 inhabitants, compared to 2.03 cases in 2010, with an average annual increase of 0.336 cases per 100,000 inhabitants (CI 95% 0.180–0.492, p = 0.001). Since 2012, men had a higher incidence of syphilis than women; the average increase among men was 0.482 cases per 100,000 inhabitants (CI 95% 0.303–0.660, p < 0.001), compared to the increase among women that was 0.178 cases per 100,000 inhabitants (CI 95% 0.017–0.339, p = 0.034), this difference was statistically significant (p = 0.010). An increase of congenital syphilis was observed, a rate of 2.93 per 100,000 newborns in the year 2014, up to 17.28 in the year 2019, with an average annual increase of 1.693 per 100,000 newborns (CI 95% 0.986–2.394, p < 0.001), as shown in Fig. 1 . Among women, the highest incidence occurred in the 20–24 years-old group with 16.77 cases per 100,000 inhabitants in 2019 and an annual increase of 0.438 per 100,000 inhabitants (CI95% 0.062–0.813; p = 0.028), followed by 15–19 years-old group with an incidence of 12.7 cases per 100,000 inhabitants in 2019 and an average annual increase of 0.693 (CI 95% 0.191–1.194; p = 0.012). Among men, the increase in incidence was concentrated in the 20-24-year-old group with a rate of 14.89 cases per 100,000 inhabitants in 2019, with an annual increase of 0.786 per 100,000 inhabitants (CI 95% 0.653–1.505; p < 0.001), followed by the group of 25–44 years with an incidence of 13.93 cases per 100,000 in 2019, with an annual increase of 0.991 cases per 100,000 (CI 95% 0.462–1.521, p = 0.002), as shown in Fig. 2. We reported a constant increase of new cases of congenital syphilis, 62 cases in the year 2010, 83 cases in the year 2015, and 372 cases in the year 2019. The states with the highest number of congenital syphilis cases in 2010 were Baja California, Colima, Chihuahua, Nuevo León, and Sonora, which reported between 6 and 17 cases; while in the year 2019 Baja California, Jalisco, Sinaloa, Sonora, and Tamaulipas presented between 20 and 79 cases of congenital syphilis. In addition, of the 32 states of Mexico, 16 did not report congenital syphilis cases in 2010, on the other hand, three states did not report congenital syphilis cases in 2019. The states of Campeche, Hidalgo, Morelos, Oaxaca, and Tlaxcala were two or fewer congenital syphilis cases from 2010 to 2019, as shown in Fig. 3 . The number of cases of congenital syphilis was correlated with the incidence of syphilis among women from 2010 to 2019 (r 2 = 0.787, p < 0.001), however, this correlation is higher when stratifying by age. Among women aged 15–19 years, each increase in an incidence unit showed an average increase of 36 new cases of congenital syphilis (slope 36.1, CI 95% 26.5–45.8, r 2 = 0.904; p < 0.001); among the group of women aged 20–24, this increase was an average of 30 cases per year (slope 30.4, CI 95% 24.8–36.0, r 2 = 0.952; p < 0.001), as shown in Fig. 4 . The correlation between syphilis and congenital syphilis by state of the Mexican Republic was evaluated, the information from 2019 of women aged 20–24 years was used, finding an r 2 = 0.621; p < 0.001. The seven states that reported an incidence of congenital syphilis greater than 40 cases per 100,000 live births are the same states that presented an incidence of syphilis greater than 40 cases per 100,000 women. States such as Morelos and Quintana Roo, reported a higher incidence of syphilis and a lower incidence of congenital syphilis, in contrast, states such as San Luis Potosí, Tabasco and Veracruz, reported a higher incidence of congenital syphilis and a lower incidence of acquired syphilis, such as shown in Fig. 5. The general mortality due to congenital syphilis in children under 1 year of age in Mexico was 0.02 per 100,000 children for the year 2012, and 0.01 for the years 2015, 2016, and 2017; for the years 2010, 2011, 2013, and 2014 we did not find information. In the review of deaths from congenital syphilis, 62 deaths were found between the years 2010 to 2017, the lowest number being in the years 2010 (5 deaths) and 2014 (1 death) and the highest in the years 2011 (10 deaths), 2015 (12 deaths) and 2017 (10 deaths). Considering the total number of deaths between 2010 and 2017 by state, the states of Baja California (7), Chihuahua (5), Jalisco (6), Sinaloa (5) and Veracruz (5), are those that presented the highest number of deaths, in contrast the states of Baja California Sur, Campeche, Guerrero, Hidalgo, Puebla, Quintana Roo, San Luis Potosí, Tlaxcala, Yucatán and Zacatecas, did not report any death from congenital syphilis during the period analyzed. Discussion According to the latest WHO estimates, the frequency of syphilis has remained constant between 2012 and 2016 with a prevalence of 0.5%, both in men and women worldwide, however, in the Americas region it was reported an increase from 0.7–0.9% in both women and men. 6 The increase in syphilis has been documented among men who have sex with men and among people living with HIV in different parts of the world. 9 – 10 In Mexico, an increase in syphilis was reported among young men between 2003 and 2013, it was hypothesized that they could be men who have sex with men, because at that time, an increase in syphilis among women had not been reported, nor an increase in congenital syphilis. 8 With the results of the present study, it is observed that the increase in syphilis among men continues, in addition, there is an increase of more than double in the incidence of syphilis among women, as well as a great increase in cases of congenital syphilis, 6 times more cases. The increase in syphilis cases among women occurs mainly in those of reproductive age, so the risk of transmission of T. pallidum during pregnancy increases, resulting in a greater number of cases and deaths from congenital syphilis. 11 PAHO in 2009 proposed the Elimination of Maternal-Child Transmission of syphilis and HIV, later adding Chagas disease and hepatitis B. 1 2,13 One of the goals is to reduce the incidence of congenital syphilis to 0.5 or less per 1,000 live births (0.005 per 100,000 live births); in current study, a lower rate of congenital syphilis was observed, however, the number of cases of congenital syphilis increased, from 62 cases in 2010 to 372 cases in 2019. Furthermore, in Mexico there is a lack of information about stillbirths due to T. pallidum , so the real incidence of congenital syphilis is underestimated. 14 To maintain the goal of reducing congenital syphilis, one of the main recommendations is to have 95% coverage of syphilis screening in pregnant women and 95% of treatment. 13 However, this percentage of coverage is far from being achieved in Mexico, according to data from National Surveys (ENSANUT-2012 and ENSANUT-2018), 15 , 16 only 43.6% of teenagers reported that they were tested for syphilis during their pregnancy, increasing to 56% in 2018, while in women aged 20–49 years, the syphilis test report increased from 39.9–62.5%. An increase in tests for syphilis during pregnancy should lead to a decrease in the number of cases of congenital syphilis, however, it is unknown whether women had access to treatment. 14 Syphilis screening during pregnancy is very important, so changes and updates to the Official Mexican Standards, as well as the Clinical Guidelines, must be considered. 17 Young people had a greater increase in syphilis, in women it was the 15-24-year-old groups that had the highest rates, while among men it was presented in the 20-44-year-old groups. In the United States, it was reported that 45% of incident STI cases are concentrated in the population aged 15–24 years. 18 It is during this stage that sexual life begins and they experiment with the use of illegal drugs, in addition to low condom use has been reported. It is necessary to continue with the emphasis of STI prevention programs in this population group. There is a great heterogeneity in the frequency of syphilis in the states of the Mexican Republic, some with a directly proportional correlation between syphilis and congenital syphilis, other states do not present an apparent correlation. Further research is needed to determine the reason for these differences, which may be at the biological level (immune status, circumcision, ectopy, coinfections), lifestyle (number of sexual partners, concurrent partners, characteristics of the partner, condom use, sexual practices and seeking medical attention), at the population level (place of residence, access to services, prevention programs, quality of care, prevalence of STIs in the locality) or characteristics of social structure (social class, age, sex or ethnicity). 19 All these variables possibly participate in the great variation of syphilis and congenital syphilis in Mexico, similar to that reported for the Herpes Simplex Virus type 2, a seroprevalence of 5.5% in the western region (Colima, Jalisco, Michoacán, Nayarit) up to 15.5% in the southwest (Chiapas, Guerrero and Oaxaca). 20 Conclusions There is an increase in syphilis among different population groups and it is concentrated in the young population of reproductive age, which cause an increase in the number of cases of congenital syphilis. Its necessary strengthened different programs, such as early detection of syphilis, treatment and follow-up of the diagnosed persons and trace of contacts, to help reduce this public health problem. Abbreviations STI sexually transmitted infection. HIV Human immunodeficiency virus WHO World Health Organization 95% CI 95% confidence intervals Declarations Ethics approval and consent to participate. Not applicable. The study is an ecological design with public information from Health Ministery from Mexico. The people could not be identified with the information that was available. Consent for publication. Not applicable Availability of data and materials. No administrative permissions were required to access the data, the information is freely accessible, at the electronic address of the Mexican Ministry of Health. The datasets used during the current study are available from the corresponding author on reasonable request. Competing interests. The authors declare that they have no competing interests. Funding. Part of this project was carried out with the support of CONACyT SALUD-2017-1-290201 Authors' contributions. SGC construct datasets, analyzes the graphs and write manuscript. AHO analyzes the information and reviews the manuscript. MOL reviews the manuscript. MASA construct figures, statistical analyzes, and write the manuscript. All authors read and approved the final manuscript. Acknowledgements. Not applicable References Peeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, Benzaken AS. Syphilis. Nat Rev Dis Primers. 2017;12:1–21. Fonollosa A, Martinez-Indart L, Artaraz J, Martinez-Berriotxoa A, Agirrebengoa K, Garcia M, et al. Clinical manifestations and outcomes of syphilis-associated uveitis in northern Spain. Ocul Immunol Inflamm. 2016;24:147–52. Syphilis. Hook EW 3. Lancet. 2017;389:1550–7. rd. . Corti M, Palmieri O, Maronna E. Sífilis secundaria maligna, forma clínica rupioide, en una enferma VIH positiva. 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Organización Panamericana de la Salud. Eliminación de la transmisión maternoinfantil del VIH y la sífilis en las Américas. Actualización 2016. Washington, D.C.: OPS; 2017. Gutiérrez JP, Rivera-Dommarco J, Shamah-Levy T, Villalpando-Hernández S, Franco A, Cuevas-Nasu L, et al. Encuesta Nacional de Salud y Nutrición 2012. Resultados Nacionales. Cuernavaca: Instituto Nacional de Salud Pública; 2012. Shamah-Levy T, Vielma-Orozco E, Heredia-Hernández O, Romero-Martínez M, Mojica-Cuevas J, Cuevas-Nasu L, et al. Encuesta Nacional de Salud y Nutrición 2018-19: Resultados Nacionales. Cuernavaca: Instituto Nacional de Salud Pública; 2020. Herrera-Ortiz A, López-Gatell H, García-Cisneros S, Cortés-Ortiz MA, Olamendi-Portugal M, Hegewisch-Taylor J, et al. Sífilis congénita en México. Análisis de las normas nacionales e internacionales desde la perspectiva del diagnóstico de laboratorio. Gac Med Mexico. 2019;155:464–72. Kreisel KM, Spicknall IH, Gargano JW, Lewis FM, Lewis RM, Markowitz LE, et al. 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Cite Share Download PDF Status: Under Review Version 2 posted Editorial decision: Major revision 18 Jul, 2021 Review # 3 received at journal 16 Jul, 2021 Review # 1 received at journal 11 Jul, 2021 Review # 2 received at journal 10 Jul, 2021 Reviewer # 3 agreed at journal 01 Jul, 2021 Reviewer # 2 agreed at journal 30 Jun, 2021 Reviewers invited by journal 30 Jun, 2021 Reviewer # 1 agreed at journal 30 Jun, 2021 Editor assigned by journal 24 Jun, 2021 Submission checks completed at journal 24 Jun, 2021 Editor invited by journal 24 Jun, 2021 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-607054","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[{"code":1,"date":"2021-06-17 14:30:47","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"articleType":"Research article","associatedPublications":[],"authors":[{"id":41374680,"identity":"83d33b3c-bf7b-48d6-8cb4-9ba370c63d3c","order_by":0,"name":"Santa García-Cisneros","email":"","orcid":"","institution":"Instituto Nacional de Salud Publica","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Santa","middleName":"","lastName":"García-Cisneros","suffix":""},{"id":41374681,"identity":"f2a370b7-1c26-493f-9681-1e6aa01c8310","order_by":1,"name":"Antonia Herrera-Ortiz","email":"","orcid":"","institution":"Instituto Nacional de Salud Publica","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Antonia","middleName":"","lastName":"Herrera-Ortiz","suffix":""},{"id":41374682,"identity":"446a24a6-63a1-4003-aa89-e063e833f06a","order_by":2,"name":"Maria Olamendi-Portugal","email":"","orcid":"","institution":"Instituto Nacional de Salud Publica","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Olamendi-Portugal","suffix":""},{"id":41374683,"identity":"ba8a8e4b-0549-4ce3-b548-f2ac5059dcd5","order_by":3,"name":"Miguel A. 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","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/2432e99226ed343c0a212278.png"},{"id":11807909,"identity":"71f4a3ca-b5ff-4739-a3dd-ebde03b42be0","added_by":"auto","created_at":"2021-07-26 14:49:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45052,"visible":true,"origin":"","legend":"Syphilis incidence stratified by sex and age, Mexico 2010-2019.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/01236b65fdd5a5a34fe262c0.png"},{"id":11807468,"identity":"6c3f9e33-1820-43c5-b4b7-d6bcdd075d4c","added_by":"auto","created_at":"2021-07-26 14:46:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":225514,"visible":true,"origin":"","legend":"New cases of congenital syphilis by state, Mexico 2010-2019. ","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/9cc24d8282a00374d3bb6a0e.png"},{"id":11807466,"identity":"88d2ee3b-3c69-42d2-af09-0982300840b7","added_by":"auto","created_at":"2021-07-26 14:46:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":29841,"visible":true,"origin":"","legend":"Syphilis among womren aged 15-24 years old and congenital syphilis, Mexico 2010-2019. ","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/e4515b1e40c26fa162d0cc63.png"},{"id":11807053,"identity":"ae5b31f0-6098-4bb0-9c64-918d6457998f","added_by":"auto","created_at":"2021-07-26 14:43:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":37635,"visible":true,"origin":"","legend":"Syphilis among women 20-24 years old and congenital syphilis, stratified by state of Mexico, year 2019. ","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/a84e2ee597c543a2a5cc2f28.png"},{"id":13705554,"identity":"b671f4fb-91a4-4741-8d69-c5539ea53c0c","added_by":"auto","created_at":"2021-09-17 13:52:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":555250,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-607054/v2/8940075b-8dcd-413f-8884-e503a604235b.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eRe-Emergence of Syphilis in Women of Reproductive Age and its Association with the Increase in Congenital Syphilis, The Case of Mexico During the Years 2010-2019\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eSyphilis is a sexually transmitted infection (STI) caused by the bacterium \u003cem\u003eTreponema pallidum subs pallidum\u003c/em\u003e. Syphilis had four stages, the primary stage begins with the chancre which appears on the glans, penis, labia majora, labia minora, the perineum, or extragenital regions (palate, anus, rectus, fingers, or tongue).\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The secondary syphilis is characterized by the systemic bacterial spread, erythematous rashes appear on palms of hands, soles of feet, chest, and back. Later there is a latency phase, without any clinical manifestation, but the non-treponemal serological tests remain positive, this stage can last up to 20 years. The infection continues and the tertiary stage is developed, affecting cardiovascular, nervous, and musculoskeletal systems.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e \u003cem\u003eT. pallidum\u003c/em\u003e can traverse the placental barrier, causing congenital syphilis. About 50% of pregnant women infected with \u003cem\u003eT. pallidum\u003c/em\u003e and not treated, transmit syphilis to their child before birth. Among people living with HIV the natural history of syphilis is altered, there are more cases with tertiary syphilis, and the cases are found in a shorter time, and the presence of syphilis increases the transmission of HIV.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to the World Health Organization (WHO) in 2016, the incidence of curable STIs in the world was estimated at 376.4\u0026nbsp;million new cases among people aged 15 to 49 years, of which 6.3\u0026nbsp;million correspond to syphilis, resulting in a worldwide incidence of 1.5 cases per 1000 inhabitants and 2.0 cases per 1000 inhabitants in America.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Furthermore, syphilis caused 200,000 stillbirths and deaths worldwide, making it one of the leading causes of newborn deaths. In the Americas region, an estimated 22,800 cases of mother-to-child transmission of syphilis were estimated, with a rate of 1.7 cases per 1,000 live births.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e In Mexico, an increase in the incidence of syphilis was detected between 2003 and 2013, concentrating among men aged 20\u0026ndash;24 years and 25\u0026ndash;44 years.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The objective of this study was to determine the trend of syphilis and congenital syphilis in Mexico, between the years 2010 to 2019, through the information available in the General Directorate of Epidemiology of the Ministry of Health of Mexico.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003eWe review the information about the incidence of syphilis, the incidence of congenital syphilis, and cases of congenital syphilis from the Morbidity Yearbooks of the General Directorate of Epidemiology of the Ministry of Health from the year 2010 to 2019. No administrative permissions were required to access the data, the information is freely accessible. Databases were formed with syphilis information and age, sex, year, and states of Mexico variables, without any variable that could identify the participants. A second database was formed, using the number of infant deaths, the year, and the state of Mexico, with information from the Morbidity and Mortality Yearbooks and the Bulletin of the Ministry of Health.\u003c/p\u003e \u003cp\u003eThe trend analysis of syphilis incidence among women, syphilis incidence among men, and congenital syphilis, from 2010 to 2019, evaluated the average change through linear regression, with 95% confidence intervals (95% CI). Subsequently, with the t-student test for slopes, the trends by age groups stratified by sex were evaluated, it was considered statistically significant p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eThe number of cases of congenital syphilis was stratified into 0\u0026ndash;2 cases, 3\u0026ndash;10 cases, 11\u0026ndash;20 cases and 21 or more cases, a comparison was made between the years 2010 and 2019 considering each state of the republic. Subsequently, the information on mortality from congenital syphilis was analyzed, with information on the year of the report and status.\u003c/p\u003e \u003cp\u003eFinally, the correlation between trends in congenital syphilis cases and incidence of syphilis in women aged 15\u0026ndash;19 years and 20\u0026ndash;24 years was evaluated, as well as the correlation between incidence of congenital syphilis and incidence of syphilis among women aged 20\u0026ndash;24 years. for each state of the republic, using the Spearman correlation test. The tests were statistically significant with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, all analyzes were carried out with the statistical program Graph Pad 10.0\u003c/p\u003e "},{"header":"Results","content":" \u003cp\u003eThe highest incidence of syphilis in the general population was observed in 2019 with 6.09 cases per 100,000 inhabitants, compared to 2.03 cases in 2010, with an average annual increase of 0.336 cases per 100,000 inhabitants (CI\u003csub\u003e95%\u003c/sub\u003e 0.180\u0026ndash;0.492, p\u0026thinsp;=\u0026thinsp;0.001). Since 2012, men had a higher incidence of syphilis than women; the average increase among men was 0.482 cases per 100,000 inhabitants (CI\u003csub\u003e95%\u003c/sub\u003e 0.303\u0026ndash;0.660, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), compared to the increase among women that was 0.178 cases per 100,000 inhabitants (CI\u003csub\u003e95%\u003c/sub\u003e 0.017\u0026ndash;0.339, p\u0026thinsp;=\u0026thinsp;0.034), this difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.010). An increase of congenital syphilis was observed, a rate of 2.93 per 100,000 newborns in the year 2014, up to 17.28 in the year 2019, with an average annual increase of 1.693 per 100,000 newborns (CI\u003csub\u003e95%\u003c/sub\u003e 0.986\u0026ndash;2.394, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong women, the highest incidence occurred in the 20\u0026ndash;24 years-old group with 16.77 cases per 100,000 inhabitants in 2019 and an annual increase of 0.438 per 100,000 inhabitants (CI95% 0.062\u0026ndash;0.813; p\u0026thinsp;=\u0026thinsp;0.028), followed by 15\u0026ndash;19 years-old group with an incidence of 12.7 cases per 100,000 inhabitants in 2019 and an average annual increase of 0.693 (CI\u003csub\u003e95%\u003c/sub\u003e 0.191\u0026ndash;1.194; p\u0026thinsp;=\u0026thinsp;0.012). Among men, the increase in incidence was concentrated in the 20-24-year-old group with a rate of 14.89 cases per 100,000 inhabitants in 2019, with an annual increase of 0.786 per 100,000 inhabitants (CI\u003csub\u003e95%\u003c/sub\u003e 0.653\u0026ndash;1.505; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), followed by the group of 25\u0026ndash;44 years with an incidence of 13.93 cases per 100,000 in 2019, with an annual increase of 0.991 cases per 100,000 (CI\u003csub\u003e95%\u003c/sub\u003e 0.462\u0026ndash;1.521, p\u0026thinsp;=\u0026thinsp;0.002), as shown in Fig.\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eWe reported a constant increase of new cases of congenital syphilis, 62 cases in the year 2010, 83 cases in the year 2015, and 372 cases in the year 2019. The states with the highest number of congenital syphilis cases in 2010 were Baja California, Colima, Chihuahua, Nuevo Le\u0026oacute;n, and Sonora, which reported between 6 and 17 cases; while in the year 2019 Baja California, Jalisco, Sinaloa, Sonora, and Tamaulipas presented between 20 and 79 cases of congenital syphilis. In addition, of the 32 states of Mexico, 16 did not report congenital syphilis cases in 2010, on the other hand, three states did not report congenital syphilis cases in 2019. The states of Campeche, Hidalgo, Morelos, Oaxaca, and Tlaxcala were two or fewer congenital syphilis cases from 2010 to 2019, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe number of cases of congenital syphilis was correlated with the incidence of syphilis among women from 2010 to 2019 (r\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.787, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), however, this correlation is higher when stratifying by age. Among women aged 15\u0026ndash;19 years, each increase in an incidence unit showed an average increase of 36 new cases of congenital syphilis (slope 36.1, CI\u003csub\u003e95%\u003c/sub\u003e 26.5\u0026ndash;45.8, r\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.904; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001); among the group of women aged 20\u0026ndash;24, this increase was an average of 30 cases per year (slope 30.4, CI\u003csub\u003e95%\u003c/sub\u003e 24.8\u0026ndash;36.0, r\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.952; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The correlation between syphilis and congenital syphilis by state of the Mexican Republic was evaluated, the information from 2019 of women aged 20\u0026ndash;24 years was used, finding an r\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.621; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. The seven states that reported an incidence of congenital syphilis greater than 40 cases per 100,000 live births are the same states that presented an incidence of syphilis greater than 40 cases per 100,000 women. States such as Morelos and Quintana Roo, reported a higher incidence of syphilis and a lower incidence of congenital syphilis, in contrast, states such as San Luis Potos\u0026iacute;, Tabasco and Veracruz, reported a higher incidence of congenital syphilis and a lower incidence of acquired syphilis, such as shown in Fig.\u0026nbsp;5.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe general mortality due to congenital syphilis in children under 1 year of age in Mexico was 0.02 per 100,000 children for the year 2012, and 0.01 for the years 2015, 2016, and 2017; for the years 2010, 2011, 2013, and 2014 we did not find information. In the review of deaths from congenital syphilis, 62 deaths were found between the years 2010 to 2017, the lowest number being in the years 2010 (5 deaths) and 2014 (1 death) and the highest in the years 2011 (10 deaths), 2015 (12 deaths) and 2017 (10 deaths). Considering the total number of deaths between 2010 and 2017 by state, the states of Baja California (7), Chihuahua (5), Jalisco (6), Sinaloa (5) and Veracruz (5), are those that presented the highest number of deaths, in contrast the states of Baja California Sur, Campeche, Guerrero, Hidalgo, Puebla, Quintana Roo, San Luis Potos\u0026iacute;, Tlaxcala, Yucat\u0026aacute;n and Zacatecas, did not report any death from congenital syphilis during the period analyzed.\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eAccording to the latest WHO estimates, the frequency of syphilis has remained constant between 2012 and 2016 with a prevalence of 0.5%, both in men and women worldwide, however, in the Americas region it was reported an increase from 0.7\u0026ndash;0.9% in both women and men.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The increase in syphilis has been documented among men who have sex with men and among people living with HIV in different parts of the world.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e In Mexico, an increase in syphilis was reported among young men between 2003 and 2013, it was hypothesized that they could be men who have sex with men, because at that time, an increase in syphilis among women had not been reported, nor an increase in congenital syphilis.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e With the results of the present study, it is observed that the increase in syphilis among men continues, in addition, there is an increase of more than double in the incidence of syphilis among women, as well as a great increase in cases of congenital syphilis, 6 times more cases.\u003c/p\u003e \u003cp\u003eThe increase in syphilis cases among women occurs mainly in those of reproductive age, so the risk of transmission of \u003cem\u003eT. pallidum\u003c/em\u003e during pregnancy increases, resulting in a greater number of cases and deaths from congenital syphilis.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e PAHO in 2009 proposed the Elimination of Maternal-Child Transmission of syphilis and HIV, later adding Chagas disease and hepatitis B. 1\u003csup\u003e2,13\u003c/sup\u003e One of the goals is to reduce the incidence of congenital syphilis to 0.5 or less per 1,000 live births (0.005 per 100,000 live births); in current study, a lower rate of congenital syphilis was observed, however, the number of cases of congenital syphilis increased, from 62 cases in 2010 to 372 cases in 2019. Furthermore, in Mexico there is a lack of information about stillbirths due to \u003cem\u003eT. pallidum\u003c/em\u003e, so the real incidence of congenital syphilis is underestimated.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo maintain the goal of reducing congenital syphilis, one of the main recommendations is to have 95% coverage of syphilis screening in pregnant women and 95% of treatment.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e However, this percentage of coverage is far from being achieved in Mexico, according to data from National Surveys (ENSANUT-2012 and ENSANUT-2018),\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e only 43.6% of teenagers reported that they were tested for syphilis during their pregnancy, increasing to 56% in 2018, while in women aged 20\u0026ndash;49 years, the syphilis test report increased from 39.9\u0026ndash;62.5%. An increase in tests for syphilis during pregnancy should lead to a decrease in the number of cases of congenital syphilis, however, it is unknown whether women had access to treatment.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Syphilis screening during pregnancy is very important, so changes and updates to the Official Mexican Standards, as well as the Clinical Guidelines, must be considered.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eYoung people had a greater increase in syphilis, in women it was the 15-24-year-old groups that had the highest rates, while among men it was presented in the 20-44-year-old groups. In the United States, it was reported that 45% of incident STI cases are concentrated in the population aged 15\u0026ndash;24 years.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e It is during this stage that sexual life begins and they experiment with the use of illegal drugs, in addition to low condom use has been reported. It is necessary to continue with the emphasis of STI prevention programs in this population group.\u003c/p\u003e \u003cp\u003eThere is a great heterogeneity in the frequency of syphilis in the states of the Mexican Republic, some with a directly proportional correlation between syphilis and congenital syphilis, other states do not present an apparent correlation. Further research is needed to determine the reason for these differences, which may be at the biological level (immune status, circumcision, ectopy, coinfections), lifestyle (number of sexual partners, concurrent partners, characteristics of the partner, condom use, sexual practices and seeking medical attention), at the population level (place of residence, access to services, prevention programs, quality of care, prevalence of STIs in the locality) or characteristics of social structure (social class, age, sex or ethnicity).\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e All these variables possibly participate in the great variation of syphilis and congenital syphilis in Mexico, similar to that reported for the Herpes Simplex Virus type 2, a seroprevalence of 5.5% in the western region (Colima, Jalisco, Michoac\u0026aacute;n, Nayarit) up to 15.5% in the southwest (Chiapas, Guerrero and Oaxaca).\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eThere is an increase in syphilis among different population groups and it is concentrated in the young population of reproductive age, which cause an increase in the number of cases of congenital syphilis. Its necessary strengthened different programs, such as early detection of syphilis, treatment and follow-up of the diagnosed persons and trace of contacts, to help reduce this public health problem.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esexually transmitted infection.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e95% CI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e95% confidence intervals\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate. Not applicable. The study is an ecological design with public information from Health Ministery from Mexico.\u0026nbsp;The people could not be identified with the information that was available.\u003c/p\u003e\n\u003cp\u003eConsent for publication. Not applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials. No administrative permissions were required to access the data, the information is freely accessible, at the electronic address of the Mexican Ministry of Health. The datasets used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests. The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding. Part of this project was carried out with the support of CONACyT SALUD-2017-1-290201\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions. SGC construct datasets, analyzes the graphs and write manuscript. AHO analyzes the information and reviews the manuscript. MOL reviews the manuscript. MASA construct figures, statistical analyzes, and write the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements. Not applicable\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePeeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, Benzaken AS. Syphilis. Nat Rev Dis Primers. 2017;12:1\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFonollosa A, Martinez-Indart L, Artaraz J, Martinez-Berriotxoa A, Agirrebengoa K, Garcia M, et al. Clinical manifestations and outcomes of syphilis-associated uveitis in northern Spain. Ocul Immunol Inflamm. 2016;24:147\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSyphilis. Hook EW 3. Lancet. 2017;389:1550\u0026ndash;7. rd. .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorti M, Palmieri O, Maronna E. S\u0026iacute;filis secundaria maligna, forma cl\u0026iacute;nica rupioide, en una enferma VIH positiva. Rara presentaci\u0026oacute;n de la l\u0026uacute;es secundaria: Presentaci\u0026oacute;n de un caso y revisi\u0026oacute;n de la literatura. Rev Argen Dermatol. 2014;95:22\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt R, Carson PJ, Jansen RJ. Resurgence of Syphilis in the United States: An Assessment of Contributing Factors. Infect Dis. 2019;16:12:1178633719883282.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97:548\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamb M, Schwartz-Benzaken A, Karem K, Matheu J, P\u0026eacute;rez F. Orientaci\u0026oacute;n para el diagn\u0026oacute;stico de la s\u0026iacute;filis en Am\u0026eacute;rica Latina y el Caribe: c\u0026oacute;mo mejorar la adopci\u0026oacute;n, interpretaci\u0026oacute;n y calidad del diagn\u0026oacute;stico en diferentes entornos cl\u0026iacute;nicos. \u003cem\u003eWashington: OPS/OMS\u003c/em\u003e, 2015; 32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHerrera-Ortiz A, Uribe-Salas FJ, Olamendi-Portugal M, Garc\u0026iacute;a-Cisneros S, Conde-Glez CJ, S\u0026aacute;nchez-Alem\u0026aacute;n MA. An\u0026aacute;lisis de la tendencia de s\u0026iacute;filis adquirida en M\u0026eacute;xico durante el periodo 2003\u0026ndash;2013. Salud Publica Mex. 2015;57:335\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LL, Chico RM, Smolak A, Newman L, Gottlieb S, Thwin SS, Brouteta N, Taylor MM. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97:548\u0026ndash;62P.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpiteri G, Unemo M, M\u0026aring;rdh O, Amato-Gauci AJ. The resurgence of syphilis in high-income countries in the 2000s: a focus on Europe. Epidemiol Infect. 2019;147:e143.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalvis AE, Arrieta A. Congenital Syphilis: A U.S. Perspective. Children (Basel). 2020;7:203.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrganizaci\u0026oacute;n Panamericana de la Salud. Iniciativa regional para la eliminaci\u0026oacute;n de la transmisi\u0026oacute;n maternoinfantil de VIH y de la s\u0026iacute;filis cong\u0026eacute;nita en Am\u0026eacute;rica Latina y el Caribe: documento conceptual. Montevideo: CLAP/SMR; 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrganizaci\u0026oacute;n Panamericana de la Salud. ETMI-PLUS: marco para la eliminaci\u0026oacute;n de la transmisi\u0026oacute;n maternoinfantil del VIH, la s\u0026iacute;filis, la hepatitis y la enfermedad de Chagas. Julio del 2017. OPS/CHA/17 \u0026ndash; 009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrganizaci\u0026oacute;n Panamericana de la Salud. Eliminaci\u0026oacute;n de la transmisi\u0026oacute;n maternoinfantil del VIH y la s\u0026iacute;filis en las Am\u0026eacute;ricas. Actualizaci\u0026oacute;n 2016. Washington, D.C.: OPS; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuti\u0026eacute;rrez JP, Rivera-Dommarco J, Shamah-Levy T, Villalpando-Hern\u0026aacute;ndez S, Franco A, Cuevas-Nasu L, et al. Encuesta Nacional de Salud y Nutrici\u0026oacute;n 2012. Resultados Nacionales. Cuernavaca: Instituto Nacional de Salud P\u0026uacute;blica; 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShamah-Levy T, Vielma-Orozco E, Heredia-Hern\u0026aacute;ndez O, Romero-Mart\u0026iacute;nez M, Mojica-Cuevas J, Cuevas-Nasu L, et al. Encuesta Nacional de Salud y Nutrici\u0026oacute;n 2018-19: Resultados Nacionales. Cuernavaca: Instituto Nacional de Salud P\u0026uacute;blica; 2020.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHerrera-Ortiz A, L\u0026oacute;pez-Gatell H, Garc\u0026iacute;a-Cisneros S, Cort\u0026eacute;s-Ortiz MA, Olamendi-Portugal M, Hegewisch-Taylor J, et al. S\u0026iacute;filis cong\u0026eacute;nita en M\u0026eacute;xico. An\u0026aacute;lisis de las normas nacionales e internacionales desde la perspectiva del diagn\u0026oacute;stico de laboratorio. Gac Med Mexico. 2019;155:464\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKreisel KM, Spicknall IH, Gargano JW, Lewis FM, Lewis RM, Markowitz LE, et al. Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2018. Sex Transm Dis. 2021 Jan 23. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0000000000001355\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAral SO. Determinants of STD epidemics: implications for phase appropriate intervention strategies. Sex Transm Infect. 2002;78(Suppl 1):i3\u0026ndash;13. Suppl 1(.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanchez-Aleman MA, Del Villar-Tapia YG, Gutierrez JP, Garcia-Cisneros S, Olamendi-Portugal ML, Herrera-Ortiz A, et al. Heterogeneity of Herpes Simplex Virus Type 2 Seroprevalence From a National Probability Survey In Mexico, 2012. Sex Transm Dis. 2018;45:111\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Syphilis, Congenital, Syphilis, Sexually Transmitted Diseases, Mexico","lastPublishedDoi":"10.21203/rs.3.rs-607054/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-607054/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Syphilis is a sexually transmitted infection that is re-emerging in different parts of the world. This infection can be transmitted during pregnancy causing neonatal syphilis. The objective of the study was to determine the trend of syphilis, congenital syphilis, and mortality from congenital syphilis among the Mexican population between the years 2010-2019. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods.\u003c/strong\u003e We formed databases about the incidence of syphilis, the incidence of congenital syphilis, cases of congenital syphilis, and deaths of congenital syphilis using information from the Morbidity and Mortality Yearbooks and the Bulletin of the Mexican Ministry of Health, considering age, sex, the states of Mexico, and year. The trend was analyzed using linear regression, the increase was estimated with 95% confidence intervals, and p\u0026lt;0.05 was considered statistically significant. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003e The incidence of syphilis increases on average 0.336 cases/100,000, being higher among women aged 15-19 years (0.693 cases). Congenital syphilis has grown, from 62 cases in the year 2010 to 372 cases in the year 2019; the cases of congenital syphilis have relation to the increase of syphilis among women aged 20-24 years. Fifty percent of the states of Mexico without cases of congenital syphilis in 2010, but only 10% in 2018. Between the years 2010 to 2017, 62 deaths from congenital syphilis were reported. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion.\u003c/strong\u003e Congenital syphilis is increasing in Mexico, as a consequence of the reemergence of syphilis among the population of reproductive age, it is necessary to attend to syphilis in various population groups.\u003c/p\u003e","manuscriptTitle":"Re-Emergence of Syphilis in Women of Reproductive Age and its Association with the Increase in Congenital Syphilis, The Case of Mexico During the Years 2010-2019","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2021-07-26 14:43:08","doi":"10.21203/rs.3.rs-607054/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-07-19T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-07-17T00:00:00+00:00","index":3,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nIn their manuscript entitled \" Re-emergence of syphilis in women of reproductive age and its association with the increase in congenital syphilis, the case of Mexico during the years 2010-2019\", García-Cisnero et al. presents an important review of the increasing case numbers of congenital syphilis across Mexico. In general, the authors prepared a nice manuscript which was well written, however, I have a few concerns.\n\nConcerns:\n1. The manuscript is lacking all figure legends.\n2. In Fig 1. Congenital syphilis incidence is presented as 0 per 100,000 for years 2010-2013. This is misleading and the scale should be adjusted to reflect the actual incidence of the disease.\n3. In the data presented in Fig. 4, a rationale was not provided for cluster the case numbers of congenital syphilis into 0-2, 3-10, 11-20, etc groups. As an example, why not use a range of 0-5, 6-10? The authors should to provide a clear rationale for the selected case number groupings and a reference.\n4. The authors make many statements in the manuscript that should be supported by references.\na. As an example of this, is the \"It is during this stage that sexual life begins and they experiment with the use of illegal drugs, in addition to…\"\n5. The authors do not state that numbers reported could be an under representation of actual case numbers because this study is an analysis of the National surveys.\n6. Please define \"PAHO\"\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2021-07-12T00:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis is a very interesting ecological analysis, with clear abd robust results. However, the design must be clear in the title and abstract and the methods should be better explained, you are missing some important points in the methods.\n\n\nTitle: Add ecological study to the title\nAbstract\nLines 16, 29 and 41: Add a colon (:) after each subheading.\nMethods and results in the abstract section are not clear.\nBackground\nLine 44, add the \",\" to the numbers 1,000 inhabitants.\nMethods:\nLines 21-30 It is not clear how were the databases constructed. Please specify what data was extracted (number of cases or incidence), proportion of males and females, or if you have individual data.\nLines 44-51, what methods did you use to compare the numbers of congenital syphilis and the mortality.\nLine 60 there is a \".\" In the wrong place.\nMissing points:\n1. Diagnostics of the regression models (i.e. distribution of residuals)\n2. In some of the figures it seems as the relationship between time (year) and syphilis incidence and especially between adult syphilis and congenital syphilis were exponential, did you test (time2 adult_syphilis2) in the models?\n3. The correlation between syphilis in males and its association with congenital syphilis.\nResults and figures:\nAre very clear, you just need to rephrase the methods section to reflect what you present in the results section.\nDiscussion\nWhat were the strengths and limitations of the study?\nYou could test some of the explanations you mention in lines 7-22. You could include in the models proportion of males, ethnic groups, some measures of income and development (i.e. state GDP or development index), some measures of access (i.e. proportion of women with screening for syphilis, ratio between doctor and inhabitants). Of course, these would be at the ecological level, but may be worth to explore.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2021-07-11T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.\n\nThe authors are describing a very important global problem. I appreciate the work that has gone into this manuscript and similar to Mexico, the United States is experiencing similar trends.\nMy questions and comments are:\n1) When the authors describe the word death, are they referring to neonatal death, stillbirth or maternal death? This is also in methods, does infant death mean intrauterine fetal demise plus neonatal demise, and how is that defined?\n2) In the last paragraph of results, are those number of deaths per 100,000 people residing in those states? I think a denominator is needed.\n3) The discussion is very well written and the stillbirth information should be updated in abstract, methods and results sections to reflect it is neonatal death (up to one year of life) not stillbirth.\n4) I do not think the mention of 2 databases were created. This is a retrospective cohort study of all data collected by the health ministry and analyzed appropriately. Not sure what is gained by mentioning 2 databases were created. Small point but in the methods, the sentence begins with we review, I believe that should be we reviewed.\n5) Can the authors mention if screening for syphilis is recommended by their health ministry Or is it mandated?\n\n6)I am thankful for the opportunity to review this manuscript and I believe with the COVID pandemic and response, public health efforts to mange reportable diseases such as syphilis has been severely compromised. All nations must work together to raise awareness and mandate testing for syphilis for all pregnant women at intake to prenatal care. Although there are differences in rates of congenital syphilis and active infection in certain countries in Mexico, one thing for certain is that T. pallidum infects fetuses consistently at each stage of infection. I believe limitations of the study needs to be included, one of which is the inherent flaws related to retrospective review of health ministry data which may be missing critical information related to the reported outcomes, including the lack of stillbirth data - which can be as high as 40% explaining differences across regions.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons after the final decision on the manuscript has been made. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2021-07-02T00:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-07-01T01:00:00+00:00","index":2,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-07-01T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-07-01T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2021-06-25T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-06-24T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-06-24T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba7e14ef-f472-4d29-83c6-c3d827e81856","owner":[],"postedDate":"July 26th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":5973128,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2021-07-26T14:43:08+00:00","versionOfRecord":[],"versionCreatedAt":"2021-07-26 14:43:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-607054","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-607054","identity":"rs-607054","version":["v2"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}