WHO method for estimating congenital syphilis to inform surveillance and service provision, Paraguay

Abstract Problem In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment. Approach The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis. Local setting The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018. Relevant changes The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV–syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones. Lessons learnt Health-care providers’ reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance.


Introduction
Vertical transmission of syphilis results in adverse birth outcomes, including fetal death (stillbirth), neonatal death, preterm birth, a low birth weight and congenital infection. 1 In Paraguay, the elimination of mother-to-child transmission of syphilis has been hampered by low coverage of maternal syphilis screening and treatment and by limited reporting of congenital syphilis. 2 Historically, incomplete surveillance data have led to the burden of congenital syphilis being underestimated in the country and to missed opportunities for infant diagnosis and treatment.
In 2014 and 2017, the World Health Organization (WHO) released criteria to validate the elimination of mother-to-child transmission of human immunodeficiency virus (HIV) and syphilis. 3,4 For syphilis, a country must have a congenital syphilis case rate of 50 or less per 100 000 live births and have reached the 95% service coverage targets outlined by WHO. 4 By December 2021, 14 countries had received validation for the elimination of mother-to-child transmission of syphilis.
The case rate target uses WHO's surveillance case definition of congenital syphilis: (i) a live birth or fetal death at > 20 weeks of gestation or > 500 g (including stillbirth) born to a woman with positive syphilis serology and without adequate syphilis treatment; or (ii) a live birth, stillbirth or child aged < 2 years born to a woman with positive syphilis serology or with unknown serostatus, and with laboratory and/or radiographic and/or clinical evidence of syphilis infection (regardless of the timing or adequacy of maternal treatment). 4

Local setting
Routine antenatal syphilis screening data from Paraguay indicated that the disease prevalence in pregnant women was 2.9% in 2016. The rate in 2018 was estimated to be 3.0% using a statistical prevalence time-trend model that combined all available antenatal syphilis surveillance data (i.e. from 2008 to 2016) with data from a sentinel survey in 2013. 5 Countryreported indicators of the elimination of mother-to-child transmission in 2018 included: (i) 100.0% of pregnant women Lessons from the field Congenital syphilis in Paraguay Katherine Heath et al.
attended an antenatal care clinic at least once; (ii) 71.2% of women who received antenatal care were screened for syphilis; and (iii) 56.2% of pregnant women diagnosed with syphilis on screening were treated (Box 1 and Fig. 1).

Approach
In 2016, WHO supported the development of a congenital syphilis estimation tool (hereafter referred to as the tool), which estimates the number of congenital syphilis cases in a country from data available on indicators of the elimination of mother-to-child transmission and additional data from users. 7 In 2019, representatives from Paraguay attended a workshop organized by WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) for countries in the WHO Region of the Americas, which included one day's training on methods for estimating syphilis prevalence. During training, country representatives: (i) estimated the current prevalence of syphilis in their countries; (ii) reviewed national data on syphilis service coverage; (iii) learned to use the WHO tool; and (iv) employed the tool to estimate national trends in the incidence of congenital syphilis. One outcome of the workshop was a factsheet detailing the congenital syphilis burden in Paraguay. 5 With the tool, the number of congenital syphilis cases in Paraguay in 2018 was estimated to be 2543 (1792 per 100 000 live births; Fig. 2). This number was substantially higher than the 280 cases (197 per 100 000 live births) reported for 2018. Both estimated and reported case numbers exceeded WHO's threshold for the elimination of mother-to-child transmission, which is 50 cases per 100 000 live births. The approximately 9-fold discrepancy between estimated and reported cases suggested underdiagnosis and underreporting. Factors identified as contributing to this discrepancy included: (i) low syphilis screening and treatment coverage during antenatal care; (ii) the failure of surveillance systems to follow pregnant women with syphilis throughout both pregnancy and delivery, which resulted in infants not being recorded as having congenital syphilis; (iii) inadequate routine syphilis testing for mothers with adverse birth outcomes, which resulted in clinical cases being underreported; and (iv) restricted testing coverage in some areas due to limited access to laboratories. Therefore, although Paraguay's case definition of congenital syphilis was similar to WHO's definition, the existing case-reporting system did not capture all cases meeting the country's definition.
In 2020, after case numbers had been estimated using the tool, Paraguay modified its information systems to track mother-infant pairs. These systems now link data on pregnant women with syphilis to delivery outcomes, which reduces the risk that syphilisexposed infants born to untreated mothers will not be recorded. According to WHO's case definition, these infants are congenital syphilis cases. Previously they were underreported. As the changes were implemented by modifying existing systems, the costs incurred were  Lessons from the field Congenital syphilis in Paraguay Katherine Heath et al.
minimal. An ongoing challenge will be sustained training of current and new staff to ensure the new systems are properly used. Between June and August 2021, training to improve the clinical diagnosis of congenital syphilis and case reporting was carried out at clinical sites in the five cities with the highest number of births and with large maternity hospitals: Asunción, Ciudad del Este, Coronel Oviedo, Encarnación and Pedro Juan Caballero. Over 600 clinical and statistics staff and staff involved in local and regional sexually transmitted infection programmes participated in 12 one-day workshops. As the workshops were added on to existing training, additional costs were minimal. Training covered the diagnosis and detection of congenital syphilis, in particular by: (i) reviewing mothers' syphilis testing and treatment records; (ii) promoting the follow-up of mother-infant pairs; and (iii) syphilis testing of mothers experiencing abortions or stillbirths. It was emphasized that any infant born to a mother with untreated syphilis should be recorded as a congenital syphilis case.
In June 2021, the four maternity hospitals that see the highest numbers of pregnant women in the country were chosen as sentinel surveillance sites to monitor WHO's indicators of the elimination of mother-to-child transmission of syphilis. Additional costs were minimal because existing local surveillance systems were used. In 2022, this surveillance system will be expanded to include more remote sentinel sites with indigenous populations by using integrated HIV resources from the Global Fund.

Relevant changes
Due to improved surveillance and comprehensive training, the number of cases of congenital syphilis reported in Paraguay increased from 280 in 2018 to 541 in 2019 and 445 in 2020. These numbers are still below the 2543 cases estimated by the tool for 2018. However, additional planned changes will further improve case reporting and service coverage. Despite increased case reporting, syphilis screening and treatment coverage in 2019 was similar to coverage in 2018: (i) 70.0% of women who received antenatal care were screened for syphilis; and (ii) 58.0% of pregnant women diagnosed with syphilis on screening were treated.
In 2021, the Pan American Health Organization procured a large quantity of rapid dual HIV-syphilis test kits and rapid plasma reagin test kits for Paraguay. These kits will enable screening and confirmatory testing to be carried out in areas with limited access to laboratories and will facilitate testing during antenatal care visits outside of laboratory hours. In addition, the health ministry in Paraguay is implementing a new national plan to eliminate motherto-child transmission of syphilis, with clear monitoring milestones and dedicated support.
Since 2019, Paraguay has been using the tool to monitor congenital syphilis cases and service coverage. Increased syphilis service coverage necessitates higher stocks of benzathine penicillin to treat newly diagnosed cases. Future use of the tool will: (i) support procurement planning by helping estimate the demand for benzathine penicillin; (ii) enable estimated and reported cases to be compared; and (iii) demonstrate the preventive effect of improved service coverage.

Lessons learnt
In 2019, the WHO congenital syphilis estimation tool highlighted congenital syphilis as a public health problem in Paraguay (Box 2), thereby revitalizing political commitment to improved surveillance and service delivery.
The tool's estimates of the number of congenital syphilis cases were based on routinely collected, national data on: (i) the prevalence of maternal syphilis; (ii) antenatal care coverage; (iii) syphilis screening during antenatal care; and (iv) maternal syphilis treatment coverage. The quality of these data is known to vary widely between countries and regions. In Paraguay, use of the tool prompted improvements in data collection, data systems and national case reporting. In addition, it demonstrated that accurate and consistent diagnosis and case reporting and rigorous syphilis surveillance were critical components of national strategies for eliminating mother-to-child transmission.
Paraguay's definition of a congenital syphilis case was similar to WHO's definition but was not being applied to Notes: The estimated congenital syphilis case rate (i.e. cases per 100 000 live births) in Paraguay was derived with the World Health Organization (WHO) congenital syphilis estimation tool, which uses data on maternal syphilis prevalence and on national service coverage of maternal syphilis screening and treatment. Congenital syphilis cases were disaggregated as: (i) adverse birth outcomes occurring in women with treated or untreated syphilis, which included stillbirths, premature or low-birth-weight infants, neonatal deaths and infants with clinical manifestations of congenital syphilis at birth (i.e. clinical congenital syphilis cases); and (ii) surveillance cases, which included all infants unaffected by an adverse birth outcome and without clinical manifestations of congenital syphilis at birth born to women with untreated syphilis. The reported case rate was obtained from national surveillance data on congenital syphilis. The threshold defined by WHO for the elimination of mother-to-child transmission of syphilis is 50 cases per 100 000 live births.
Lessons from the field Congenital syphilis in Paraguay Katherine Heath et al.
identify potential cases. Subsequently, case reporting was improved by training on syphilis detection and case management, which demonstrated that ensuring national surveillance systems align with WHO's definition is a priority for tracking progress towards the elimination of mother-to-child transmission. Scaling up rapid dual HIV-syphilis and rapid plasma reagin testing in Paraguay, in accordance with WHO's recommendations, 8 will result in higher detection rates and greater demand for benzathine penicillin. The ongoing incorporation of data on antenatal testing and treatment coverage and on maternal syphilis prevalence will enable the tool to provide estimates of the demand for benzathine penicillin, which is crucial for preventing medicine shortages. 9 An ongoing challenge for highprevalence countries is addressing syphilis transmission in general. Public health systems will have to prioritize syphilis prevention in both the general population and in high-risk groups alongside ensuring adequate clinical services. Reducing the prevalence of syphilis in the general population, including pregnant women, will have downstream effects for congenital syphilis. 10 Other countries can use WHO's freely available congenital syphilis estimation tool to demonstrate that highquality data on antenatal care service coverage are important for syphilis surveillance and prevention programmes. In low-burden countries, such as Malaysia, Sri Lanka, the Maldives and Thailand, the tool has been used to validate the sustained elimination of mother-tochild transmission. [11][12][13][14] Recently, WHO incorporated the tool into new guidance on eliminating mother-to-child transmission of syphilis and, 15

. Summary of main lessons learnt
• Limited application of Paraguay's case definition for congenital syphilis and partial misalignment with WHO's case definition led to the underreporting of cases. • Use of the WHO congenital syphilis estimation tool revealed a discrepancy between estimated and reported case numbers in Paraguay, thereby highlighting congenital syphilis as a national public health problem. • Use of the WHO estimation tool resulted in: (i) the strengthening of Paraguay's information systems; (ii) the provision of training to improve congenital syphilis diagnosis and case reporting; (iii) the procurement of additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase testing capacity; and (iv) improvement in the monitoring of syphilis case rates and service coverage.
Lessons from the field

Lessons from the field Congenital syphilis in Paraguay
Katherine Heath et al.