Syphilis caused by Treponema pallidum (TP) is one of the most common sexually transmitted diseases worldwide. Congenital syphilis (CS) is caused by mother-to-child transmission (MTCT) of TP infection during pregnancy. MTCT of syphilis during pregnancy can lead to serious fetal outcomes in the second or third trimester, including stillbirth, neonatal death, preterm birth, low birth weight, and congenital infection in infants.1–3 In 2007, the World Health Organization (WHO) launched the global elimination of CS initiative, with the goal of reducing MTCT of syphilis to a sufficiently low level that CS was no longer a public health problem.4 In 2010, the Pan American Health Organization initiated a regional strategy for the Americas with the broader goal of the dual elimination of MTCT (EMTCT) of syphilis and human immunodeficiency virus (HIV) by integrating the screening programs for both infections into routine antenatal care (ANC).5 The strategy, which was updated in 2015, aims to detect and treat syphilis and HIV in early pregnancy so that infants will be born free of these diseases.6 In 2015, Cuba became the first country to be validated by the WHO for having achieved the EMTCT of syphilis. To date, 11 countries and territories, including Cuba, Thailand, Belarus, Moldova, Anguilla, Antigua and Barbuda, Bermuda, the Cayman Islands, Montserrat, St Kitts and Nevis, and Malaysia, have been validated as having eliminated MTCT of syphilis.7–10 However, after 10 years of effort, over 300,000 fetal and neonatal deaths each year were still attributed to syphilis, with 215,000 additional infants placed at increased risk of early death.11 From 2012 to 2016, the CS rate increased from 8.4 to 15.7 cases per 100,000 live births, representing an 87% increase in the USA.12 Many countries and territories have a high maternal syphilis prevalence and high CS prevalence.2 The maternal syphilis prevalence and CS prevalence in some countries and territories are increasing.13–17 To achieve global CS elimination, early syphilis screening and treatment in ANC, improving partner management, and reducing syphilis prevalence in the general population will be required.2
The global burden of CS
It is estimated that the global maternal syphilis prevalence was 0.69% and 0.70% in 2016 and 2012.2 Kuznik et al. estimated the public health burden resulting from adverse pregnancy outcomes due to syphilis infection among pregnant women not screened for syphilis in 43 countries in Sub-Saharan Africa. The estimated incidence of adverse pregnancy outcomes (APOs) was 205,901 per year, including stillbirth, neonatal death, low birth weight, and CS, resulting in approximately 12.5 million disability-adjusted life years (DALYs). Countries with the greatest burden are (in DALYs, millions) the Democratic Republic of the Congo (1.809), Nigeria (1.598), Ethiopia (1.466), and Tanzania (0.961).18Figure 1 shows that the estimated global maternal syphilis prevalence in 2016. The maternal syphilis prevalence was high in many countries, most of which are developing countries.
Compared with the worldwide decrease in CS, maternal prevalence remained stable and in some countries increased. In the USA, there were 0.9 cases of maternal primary and secondary syphilis infection per 100,000 women and 8.4 cases of CS per 100,000 live births in 2012. The rate of maternal primary and secondary syphilis infection increased to 1.9 per 100,000 women and 15.7 cases of CS per 100,000 live births in 2016.12 The CS rate of 9.2 cases per 100,000 live births in 2013 was the first increase since 2008. During 2013–2014, the rate increased 27.2%; during 2014–2015, the rate increased 6.0%, and then increased 27.6% during 2015–2016. There were 628 cases of CS reported in 2016 compared with 492 cases in 2015. The rates of CS were highest among Blacks African Americans (43.1 cases per 100,000 live births), followed by American Indians/Alaska Natives (31.6 cases per 100,000 live births), and Hispanics (20.5 cases per 100,000 live births) in 2016.12 In Brazil, the prevalence of maternal syphilis was 4.1% in 2012, 3.1% in 2013 and 5% in 2014.13 From 2007 to 2014, the annual incidence rate of CS in Brazil increased from 2.9 to 8.1 cases per 1,000 live births.14 Silva Neto reported maternal syphilis detection rates of 17.2 (2010), 16.3 (2011), 21.9 (2012), 17.5 (2013), and 31.4 (2014) cases per 1,000 live births in Brazil. The CS incidence rates were 15.1 (2010), 12.1 (2011), 15.6 (2012), 9.1 (2013), and 22.3 (2014) cases per 1000 live births.15 In Hungary, 148 women were seropositive during this 4-year period. Seroprevalence was 2‰ in 2013, 2.7‰ in 2014, 3.4‰ in 2015, and 3‰ in 2016. In Mongolia, syphilis prevalence was estimated to have risen from 1.7% in 2000 to 3.0% in 2016.17 In Canada, from 2010 to 2015, the rate of syphilis was from 5.0 to 9.3 cases per 100,000 live births.19 In the Netherlands, from 2014 to 2015, the CS rate was from 0–1.14 to 0–0.59 cases per 100,000 live births.20
Maternal syphilis screening, diagnosis, and treatment
The screening and diagnosis for maternal syphilis and CS were reviewed by several reviews and guidelines.21–25 Serodiagnostic tests are the only means for screening asymptomatic individuals and are the most commonly used methods to diagnose symptomatic patients. Serodiagnostic tests for syphilis can be broadly categorized into nontreponemal tests (NTTs), including rapid plasma reagin (RPR) and the venereal disease research laboratory test, which detects both IgM and IgG antibodies against cardiolipins released from damaged host cells during infection, and treponemal tests (TTs), including all assays that detect IgM and IgG antibodies specific to TP, such as treponema pallidum particle assay (TPPA). NTT antibody titers might correlate with disease activity and are used to follow the treatment response. The TTs generally remain reactive for life following clearance of the infection. WHO and several national guidelines all recommend universal syphilis screening for all pregnant women at the first prenatal visit. In addition, for women who are at high risk for syphilis or live in areas of high syphilis morbidity, these organizations recommend repeat screening early in the third trimester and again at delivery. After delivery, neonates should not be discharged from the health facility unless the serological status of the mother has been determined at least once during pregnancy and preferably again at delivery.21–25 Quantitative maternal nontreponemal titer, especially when >1:8, might be a marker of ongoing infection. Figure 2 shows chancres and the maculopapular skin rash in patients with syphilis and neonatal CS.
Serological diagnosis for syphilis is based on the detection of both nontreponemal antibodies and treponemal-specific antibodies. When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for CS. However, this evaluation should not delay therapy. Sonographic signs of fetal or placental syphilis indicate a greater risk for fetal treatment failure; cases with these signs should be managed in consultation with obstetric specialists.
All women who have syphilis should be offered testing for other sexually transmitted disease. Figure 3 shows the testing algorithms for syphilis screening and diagnosis in pregnant women. Hersh et al. found that compared to screening once, repeat screening all women during the first and third trimesters is cost-effective.26
The long-acting penicillin preparations such as benzathine penicillin G (BPG) are the preferred therapies for most patients with syphilis. BPG is highly efficacious during pregnancy and remains the main recommended treatment for maternal syphilis and prevention of CS. Treatment of spirochete infections can result in the Jarisch-Herxheimer reaction, which mainly occurs during the first 24 hours of treatment in primary and secondary disease. Data supporting the use of alternatives to penicillin in the treatment of syphilis in pregnancy are limited. Table 1 shows the recommended treatment regimens for syphilis during pregnancy according to the stages of the disease. After maternal syphilotherapy, follow-up NTT titers are assessed monthly to ensure they are not increasing fourfold, which is considered a clinically significant titer change.21–24
According to the China national guidelines, syphilis-seropositive pregnant women should be provided with two courses of syphilis treatment for prevention of MTCT.27,28 A single complete course includes either benzathine penicillin 2.4 million units intramuscularly per week for three consecutive weeks or procaine penicillin 0.8 million units intramuscularly daily for 15 consecutive days. Two recent studies showed that women who received one course of penicillin and women who received two courses of penicillin had a similar risk of APOs and suggest that one course of benzathine penicillin injection may be reasonable. The limitation of the two studies is that they were not prospective clinical trials.29,30 Regular follow-up should be conducted after the treatment. A monthly RPR or toluidine red unheated serum test (TRUST) for observation of titer changes should be conducted to determine whether there is a recurrence or reinfection. During the follow-up, if the titer of the RPR or TRUST test increases or the result changes from negative to positive, reinfection or recurrence may occur, and a course of treatment for syphilis should be started immediately. Whether the maternal treatment is adequate depends upon the sufficient duration with correct doses. Maternal treatment less than 30 days before delivery means that the efficacy is not optimal and infants are likely to be infected.
Sexual partner who have had sexual contact with a person who receives a diagnosis of primary, secondary, or early latent syphilis within 90 days preceding the diagnosis should be treated presumptively for early syphilis, even if the serological test results are negative.31
The risk, diagnosis, and treatment of CS
The risk for CS is mainly related to three factors: (1) high maternal prevalence, (2) low coverage of ANC services, and (3) fetal treatment failure. The fetal treatment failure is defined as the diagnosis of CS despite adequate maternal treatment. Risk factors for fetal treatment failure mainly include high maternal titers or earlier stage of disease.32–36 In many CS cases, mothers with syphilis have not received therapy when they deliver their children. In the USA, among 628 reported cases of CS in 2016, 52.2% had documentation that they received any prenatal care at least 30 days prior to delivery; 4.8% received prenatal care but the first visit occurred fewer than 30 days before delivery; 26.4% did not receive any prenatal care; and 16.6%had unknown prenatal care status.37 Matthias et al. studied 710 pregnant women with syphilis in Louisiana and Florida linked to 155 CS cases. Three hundred and seventy (52%) pregnant women with syphilis had early-stage syphilis or high-titer late or unknown duration-latent syphilis, and 70% of the total was linked to CS cases. Screening in the first two trimesters identified 513 pregnant women who tested positive for syphilis, and 92% potential CS cases were averted. One hundred and nine pregnant women tested positive for syphilis in the third trimester, and 78% had babies without CS. During their pregnancies, 12% women tested negative at least once, and 65% had babies with CS. Thirty-nine women had no reported syphilis screening 30 days or longer before delivery.38 In California, during the selected period, 2498 women were diagnosed as having syphilis, and 17% were linked to birth records; 38% were defined as CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. The CS prevention cascade showed decrements of 5%–11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented.39 A total of 15,884 pregnant women with syphilis infection delivered in China in 2013. Of the infected women, 79.1% attended ANC at or before 37 gestational weeks; however, 55.4% received no treatment or initiated the treatment after 37 gestational weeks. Approximately 14.0% of women suffered serious APOs, including stillbirth/neonatal death, preterm delivery/low birth weight, or CS in newborns. High maternal titer (≥1:64) and late treatment (>37 gestational weeks)/nontreatment were significantly associated with an increased risk of CS.40 In a total of 61 cases of MTCT in the syphilis study, 95.08% (58 cases) of mothers experienced prenatal care, and 54.10% (33 cases) were diagnosed with gestational syphilis during this period.41 Su found no or inadequate treatment for maternal syphilis, <10 prenatal visits, and maternal nontreponemal titer ≥1:8 increased the likelihood of a CS dead case; infants with CS born alive at <28 weeks gestation or born weighing <1500 g were at greatly increased risk of death.42 Early detection and treatment of syphilis during pregnancy is the clinical mainstay of CS prevention. More broadly, prevention of syphilis and access to highly effective contraception among all women of reproductive age are essential elements for the prevention of CS.43
The diagnosis of CS cannot be established simply based on a positive antibody tests because of the maternal IgG may transfer through placental. The CS may be diagnosed if any of the following criteria are met: (1) a positive dark-field test of lesions or body fluid, (2) a positive TP IgM test, (3) a serum quantitative nontreponemal serological titer that is fourfold greater than the mother's titer and a positive TP, (4) an infant had sero-reverted NTTs or a increased serum quantitative nontreponemal serological titer during follow-up, (5) an infant had a reactive TPPA test at age 18 months.27–30,38–40 Ultrasound abnormalities suggestive of fetal syphilis can be seen at >20 weeks and in all stages of maternal syphilis. One study found that 31% of infected gravidas had evidence of fetal syphilis on pretreatment ultrasound. These abnormalities include hepatomegaly (80%), an elevated peak systolic velocity of the middle cerebral artery (MCA) by doppler ultrasound indicative of fetal anemia (33%), placentomegaly (27%), polyhydramnios (12%), ascites (10%), and fetal hydrops.44 No mother or newborn infant should leave the hospital without the maternal serological status having been documented at least once during pregnancy and preferably again at delivery if at risk. The misdiagnosis and over-reporting of CS and the inadequate management of neonatal of maternal syphilis have also been reported. Wu et al. studied infants with CS who were followed for 12 months. All RPR tests and TP particle agglutination assays became negative between 3 and 10 months after birth.45 Such misdiagnosis and over-reporting of CS have also occurred in other areas.46,47 Ye et al. reported 50.9% (56 out of 110 cases) over-reporting of CS.
Stafford et al. studied the neonatal data of maternal syphilis. Only 15% of fetuses underwent antenatal sonographic evaluation for CS, and one had findings consistent with congenital infection as evidenced by elevated MCA velocities before treatment. Twelve newborns were diagnosed as highly likely to have CS and were treated with a full 10-day dose of penicillin. Nine percent of newborns were symptomatic at birth; however, only 83.3% of the symptomatic newborns were admitted to the neonatal intensive care unit. Only 20% of infants were adequately treated with either a single dose or an extended penicillin regimen if the mother was not adequately treated.48
The recommended regimens for CS are as follows: aqueous crystalline penicillin G administered as 50,000 units/kg/dose intravenous every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days; or Procaine penicillin G 50,000 units/kg/dose intramuscular in a single daily dose for 10 days.21–24
Prioritizing CS control in China
In response to the resurgent syphilis epidemic, the Chinese Ministry of Health announced a comprehensive 10 Year National Syphilis Prevention and Control Plan. Averting CS cases is at the center of this mandate, with explicit strategies that focus on improving prenatal syphilis screening coverage, increasing treatment rates in infected pregnant women, and increasing syphilis awareness among adults.49,50 In Shenzhen, China, from 2007 to 2012, 279,334 pregnant women were screened, and 0.3% women were identified as infected with syphilis. The patients were given three injections of 2.4 million units of benzathine penicillin at weekly intervals. Among infants born to mothers with syphilis, 8.2% were diagnosed with CS, and 24.7% were diagnosed with APOs.51 From 2011 to 2016, a total of 4746 matched cases of syphilis-seropositive mothers and their infants were included for analyses, and 162 infants were diagnosed with CS, providing an overall incidence of 3.41%. The treatment for syphilis-seropositive pregnant women was categorized into adequate treatment before pregnancy or no treatment before pregnancy, two courses treatment during pregnancy or one-course treatment during pregnancy, treatment initiation before 28 weeks of gestation or treatment initiation ≥28 weeks of gestation. One-course treatment includes three injections of 2.4 million units of benzathine penicillin at weekly intervals. Adequate treatment means at least has one course treatment. Among infants born to syphilis-seropositive women who had syphilis and were adequate treatment, the incidence was 0.22%. There were 159 cases of CS occurring in 3519 infants born to women who were syphilis-seropositive during their pregnancies, for an incidence of 4.52%. The incidence of CS was 1.82% and 11.90% among infants born to women treatment initiation before 28 weeks of gestation compared with those treatment initiation ≥28 weeks of gestation, other antibiotics, or those untreated. The incidence rates were 0.22% and 0.59% in infants born to women treated with two courses and one course of treatment.29 Based on another study from Shenzhen, the screened rate among pregnant women increased from 89.8% in 2002 to 97.4% in 2011; The incidence of CS decreased from 115/100,000 in 2002 to 10/100,000 (live births) in 2011.52 In Beijing, China, among 807 maternal syphilis cases, the maternal syphilis ratios increased from 1.1% (in 2013) to 1.4% (in 2015) of live births, while APOs, including CS (1.3%–0.4%), neonatal deaths (1.3%–0%), and neonatal asphyxia (0.9%–0%), decreased. The incidence of APO (excluding premature or low birth weight) was 5.63%, 3.17%, and 2.62% in the three years. Both prevention and treatment interventions increased, including antenatal testing (93.5%–93.9%), any treatment (76.6%–85.2%), adequate treatment (51.1%–65.1%), and treatment initiated in the first trimester (30.7%–42.8%).53 In Shanghai, China, the prevalence of seropositivity for maternal syphilis ranged from 0.20% to 0.38% during 2001–2015.54
In 2010, a national program that integrated and standardized prevention of mother-to-child transmission (PMTCT) efforts for HIV, syphilis and hepatitis B virus was implemented. At participating ANC clinics, pregnant women were offered all three tests concurrently and free of charge. Further interventions, such as free treatment, prophylaxis, and testing for mothers and their children, were provided for HIV and syphilis. Integrated PMTCT services proved to be feasible and effective, and they are now part of the routine maternal and child health services provided to infected women.49,50,55 In 2015, the National Health Commission of China implemented the national prevention of mother-to-child transmission of HIV, syphilis, and hepatitis B project.27,28 The project comprehensively implements national prevention of mother to child transmission of acquired immune deficiency syndrome (AIDS) syphilis and hepatitis B. The prevention of mother to child transmission of AIDS syphilis and hepatitis B services are free of charge. Specific levels of service delivery also need to be met to accomplish EMTCT of syphilis. The process targets: (1) ANC coverage (at least one visit) of ≥90%, (2) coverage of syphilis testing of pregnant women of ≥90%, (3) treatment of syphilis-seropositive pregnant women of ≥90%.27,28 The project emphasizes the following key issues: (1) strengthening leadership, (2) widely publicizing propagation and participation, (3) improving the service network and capacity, and (4) having standardized protocols. This is consistent with the WHO's four-pillar strategy for eliminating CS: (1) ensure advocacy and political commitment, (2) increase access to and quality of services, (3) screen and treat pregnant women and partners, (4) establish surveillance, monitoring, and evaluation. It is estimated that the maternal syphilis prevalence in China from 2012 to 2016 decreased from 0.27% to 0.16%.2 In China, between 2011 and 2017, the number of reported CS cases declined from 13,294 to 3846. In 2017, the coverage of syphilis screening test among pregnant women was over 99.5%.56
The problems and solutions
There are several challenges in preventing CS from both pregnant women and their health care providers. These problems include that prenatal care lack or delay, syphilis management flaws from health care providers, lack of basic information, and awareness about maternal syphilis and CS by public.57–65
In Brazil, inadequate prenatal care was observed in 37.9% of pregnant women. Only 34.2% of patients completed the treatment according to the guidelines issued by the Ministry of Health of Brazil, and 19.8% of the partners of the patients underwent adequate syphilis treatment; 13.8% couples underwent correct treatment.58
From 2010 to 2014, the infant mortality rate of CS was 16.3 per 100,000 live births. Of the 414 cases reported to the Mortality Information System (Sistema de Informacao sobre Mortalidae) as deaths possibly caused by CS, 10.6% presented CS as the underlying cause. There was an 89.4% underreporting of deaths. Perinatal deaths and fetal deaths of CS accounted for 87.7% and 73.9% of total deaths, respectively.59
In the USA, approximately 11.8% of states do not mandate prenatal syphilis screening.60 Nkamba et al. studied the barriers and facilitators to the implementation of antenatal syphilis screening and treatment for the prevention of CS in the Democratic Republic of Congo and Zambia. The barriers were: (1) system level: fragmentation of the health care system, existence of ANC guidelines in conflict with proposed interventions, poor accessibility to clinics (geographical and functional), staff and product shortages at the primary care clinics, (2) health care provider level: lack of knowledge and training about evolving best practices, reservations regarding same-day screening and treatment, (3) pregnant women level: late enrollment in ANC, lack of knowledge about consequences, and treatment of syphilis, and stigma. Based on these results, Nkamba et al. developed recommendations for the design of the preventive congenital syphilis intervention trial.61
Many flaws have been identified at primary health centers regarding the management of syphilis during pregnancy. Accessing testing and treatment is difficult, and there are no standardized strategies to notify the partner. The responsibility for notifying partners is transferred to the women, and counseling does not offer proper guidance nor sufficient emotional support to help these patients.62 In China, syphilis mainly managed in dermatiology and venereology department, which arised from China medical education and clinical practice. Until currently there is no full maternal-infant medicine training program. To have obstetricians manage the maternal syphilis is also a challenge. Only 80% of maternal syphilis was treated before delivery.56 One of the reasons of low and delay maternal syphilis therapy rate in China may be the patients transfer from obstetricians to dermatiology and venereology specialist.
Communicating the burden of CS has been challenging because adverse health outcomes such as stillbirth, are not always attributed to CS. Many policymakers and health professionals seem unaware of the number of babies who die needlessly of syphilis.63 The awareness efforts have been unsuccessful because of the stigma surrounding syphilis and the poor visibility of CS gives the perception that CS is not a major public health problem.64 In some countries and territories, there has been a shortage of benzathine penicillin for the PMTCT of syphilis.65
Many efforts have been made to solve the problems. These include that dual EMTCT of both HIV and syphilis or triple EMTCT of HIV, syphilis and hepatitis B, WHO country validation of EMTCT of syphilis and HIV, set up a CS case review board and a National Day to Combat Syphilis and Congenital Syphilis and so on.27,28,66–80
In 2010, China made a commitment to the dual EMTCT of HIV and syphilis, providing an important opportunity for the MTCT of syphilis to be prioritized in policy and resource allocation at national and subnational levels.66 A workshop, co-convened by WHO and partners, was held in June 2011 for six Sub-Saharan African countries with a strong interest in dual elimination to support the development of action plans addressing the opportunities and urgency of joint program planning.67
Some regional and country-led initiatives, as well as encouragement by external partners, led the WHO to promote integration programs for dual EMTCT of both HIV and syphilis.68 The first multiplex rapid diagnostic test (RDT) for the detection of HIV and TP (dual HIV/syphilis RDT) was listed on the WHO list of prequalified in vitro diagnostic products in 2015.69 The dual HIV/syphilis RDT is currently used in many countries.69–73 Gliddon et al. made a meta-analysis of evaluating the dual point-of-care tests for HIV and syphilis and found that dual RDTs were highly acceptable. The dual RDTs for HIV and syphilis could be implemented in national programs and clinical practices by policy-makers.74
The National Health Commission of China implemented national prevention of mother-to-child transmission of HIV, syphilis and hepatitis B in 2015.27,28 In 2018, the Regional Framework for the Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018–2030 proposed to offer a coordinated approach towards achieving the EMTCT of HIV, hepatitis B and syphilis and provide guidance for decision-makers, managers and health care professionals. The WHO proposed priority actions for a coordinated approach to triple elimination, supported by three pillars: (1) policy, (2) service delivery, and (3) monitoring and evaluation.75 Several studies have demonstrated that the integrated approach for triple EMTCT of HIV, hepatitis B, and syphilis is highly effective and cost-effective.76,77
Because of high CS rates, the Louisiana Department of Health Sexually Transmitted Disease/Human Immunodeficiency Virus Program formed CS case review boards to study CS cases. Review boards provided recommendations to health care providers which enhanced the prevention effectiveness. Many CS cases can be prevented by screening and treating women early in pregnancy and rescreening early in the third trimester to identify infections acquired during pregnancy.78
In Brazil, a National Day to Combat Syphilis and Congenital Syphilis (third Saturday in October) was designated to further raise public awareness of the problem and to promote educational activities on sexuality and sexually transmitted infections.79
Several tools, such as antenatal-care syphilis testing recommendations; rapid HIV and syphilis test interim guidance; current and projected use of BPG in maternal syphilis; syphilis treatment guidelines; CS case definition; staff training on BPG administration; and penicillin desensitization protocols may aid the screening, treatment, and elimination of CS.64 The country validation of EMTCT of syphilis and HIV launched by the WHO may greatly speed up the EMTCT of syphilis action and decrease CS prevalence. The criteria for the validation of EMTCT include high levels of ANC access and syphilis testing and treatment for pregnant women and their infants.
The minimum EMTCT impact targets are: ≤50 cases of CS per 100,000 live births and specific levels of service delivery also need to be met to accomplish EMTCT of syphilis. The process targets: (1) ANC coverage (at least one visit) of ≥95%, (2) coverage of syphilis testing of pregnant women of ≥95%, (3) treatment of syphilis-seropositive pregnant women of ≥95%.9,10 During the validation process, a country must demonstrate that all pregnant women and infants exposed to syphilis have universal access to essential interventions to prevent MTCT. The quality of interventions, including laboratory services, is also assessed. Financial barriers and financial support for vulnerable populations are evaluated to ensure equitable access. The lessons learned from countries that have achieved elimination should be widely shared.80
The authors acknowledge Xiang-Sheng Chen from the National Center for STD Control of Chinese Academy of Medical Sciences for his criticizing review and helpful discussion on this article.
This research was supported by the Shenzhen Science and Technology Plan (JCYJ20180228162311024), Shenzhen Health System Key Discipline Construction Capacity Enhancement Project (SZXJ201606001).
Conflicts of Interest
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