Detection of gestational and congenital syphilis in Paraná state, Brazil, 2007-2021: a time series analysis Translated title: Detección de sífilis gestacional y congénita en Paraná, Brasil, 2007-2021: análisis de series temporales Translated title: Detecção de sífilis gestacional e congênita no Paraná, 2007-2021: análise de séries temporais
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Abstract
Objective:
To describe temporal trends in the detection rates of gestational and
congenital syphilis, by maternal age and health macro-region of the state of
Paraná, Brazil, 2007-2021.
Methods:
This was a time-series study using surveillance data; the trend analysis was
performed by means of joinpoint regression, and average annual percent
change (AAPC) and 95% confidence intervals (95%CI) were estimated.
Results:
An increase in statewide detection of gestational syphilis (AAPC = 21.7;
95%CI 17.7; 32.8) and congenital syphilis (AAPC = 14.8; 95%CI 13.0; 19.7)
was found; an increase was also found in the health macro-regions, with the
Northwest (gestational, AAPC = 26.1; 95%CI 23.4; 31.6) and North
(congenital, AAPC = 23.8; 95%CI 18.8; 48.9) macro-regions standing out;
statewide rising trends were observed for young women [gestational, AAPC =
26.2 (95%CI 22.4; 40.6); congenital, AAPC = 19.4 (95%CI 17.6; 21.8)] and
adult women [gestational, AAPC = 21.3 (95%CI 16.9; 31.9); congenital, AAPC =
13.7 (95%CI 11.9; 19.3)].
Conclusion:
Maternal and child syphilis detection rates increased in the state,
regardless of maternal age and health macro-region.
Study contributions
Main results
Increasing trends were found for the detection rates of gestational and
congenital syphilis in Paraná state and its health macro-regions, including
in the analysis stratified by maternal age group; however, there was a
decline during the COVID-19 period.
Implications for services
There is a need for strategic and immediate action by the state health
services, focusing on expanding access and linkage to care, in order to
ensure maternal and child well-being and reverse the rising trends
observed.
Perspectives
Prevention and control actions towards the elimination of syphilis are needed
to overcome these obstacles, directing efforts towards strengthening health
education, early detection and appropriate treatment for pregnant women and
their partners.
Resumen
Objetivo:
Describir las tendencias temporales en las tasas de detección de sífilis
gestacional y congénita, por grupo de edad materna y macrorregión de salud
de Paraná, 2007-2021.
Métodos:
Estudio de series temporales utilizando datos de vigilancia; se realizó
análisis de tendencia mediante regresión segmentada, estimando cambios
porcentuales anuales promedio (CPAP) e intervalos de confianza del 95%
(IC
95%).
Resultados:
Se identificaron aumentos en la detección estatal de sífilis gestacional
(CPAP = 21,7; IC
95% 17,7;32,8) y congénita (CPAP = 14,8;
IC
95% 13,0;19,7); las macrorregiones mostraron incrementos,
destacándose la Noroeste (gestacional, CPAP = 26,1; IC
95%
23,4;31,6) y la Norte (congénita, CPAP = 23,8; IC
95% 18,8;48,9);
las tendencias estatales fueron crecientes para mujeres jóvenes
[gestacional, CPAP = 26,2 (IC
95% 22,4;40,6); congénita, CPAP =
19,4 (IC
95% 17,6;21,8)] y adultas [gestacional, CPAP = 21,3
(IC
95% 16,9;31,9); congénita, CPAP = 13,7 (IC
95%
11,9;19,3)].
Conclusión:
Las tasas de detección de sífilis materno-infantil estuvieron en aumento en
el estado, independientemente de la edad materna y la macrorregión de
salud.
Resumo
Objetivo:
Descrever as tendências temporais nas taxas de detecção de sífilis
gestacional e congênita, por faixa etária materna e macrorregião de saúde do
Paraná, Brasil, 2007-2021.
Métodos:
Estudo de séries temporais, utilizando-se dados de vigilância; realizou-se
análise de tendência por regressão segmentada, sendo estimadas variações
percentuais anuais médias (VPAM) e intervalos de confiança de 95%
(IC
95%).
Resultados:
Foram identificados acréscimos na detecção estadual de sífilis gestacional
(VPAM = 21,7; IC
95% 17,7;32,8) e congênita (VPAM = 14,8;
IC
95% 13,0;19,7); as macrorregiões de saúde registraram
incrementos, destacando-se as macrorregiões Noroeste (gestacional, VPAM =
26,1; IC
95% 23,4;31,6) e Norte (congênita, VPAM = 23,8;
IC
95% 18,8;48,9); as tendências estaduais foram crescentes
para mulheres jovens [gestacional, VPAM = 26,2 (IC
95% 22,4;40,6);
congênita, VPAM = 19,4 (IC
95% 17,6;21,8)] e mulheres adultas
[gestacional, VPAM = 21,3 (IC
95% 16,9;31,9); congênita, VPAM =
13,7 (IC
95% 11,9;19,3)].
Conclusão:
As taxas de detecção de sífilis materno-infantil foram ascendentes no
estado, independentemente da idade materna e da macrorregião de saúde.
Congenital syphilis is an infection with Treponema pallidum in an infant or fetus, acquired during pregnancy from a mother with untreated or inadequately treated syphilis. Congenital syphilis can cause miscarriage, stillbirth, or early infant death, and infected infants can experience lifelong physical and neurologic problems. Although timely identification and treatment of maternal syphilis during pregnancy can prevent congenital syphilis ( 1 , 2 ), the number of reported congenital syphilis cases in the United States increased 261% during 2013–2018, from 362 to 1,306. Among reported congenital syphilis cases during 2018, a total of 94 resulted in stillbirths or early infant deaths ( 3 ). Using 2018 national congenital syphilis surveillance data and a previously developed framework ( 4 ), CDC identified missed opportunities for congenital syphilis prevention. Nationally, the most commonly missed prevention opportunities were a lack of adequate maternal treatment despite the timely diagnosis of syphilis (30.7%) and a lack of timely prenatal care (28.2%), with variation by geographic region. Congenital syphilis prevention involves syphilis prevention for women and their partners and timely identification and treatment of pregnant women with syphilis. Preventing continued increases in congenital syphilis requires reducing barriers to family planning and prenatal care, ensuring syphilis screening at the first prenatal visit with rescreening at 28 weeks’ gestation and at delivery, as indicated, and adequately treating pregnant women with syphilis ( 2 ). Congenital syphilis prevention strategies that implement tailored public health and health care interventions to address missed opportunities can have substantial public health impact. Congenital syphilis is a reportable condition in all 50 states and the District of Columbia and is nationally notifiable; case reports are sent voluntarily to CDC through the National Notifiable Diseases Surveillance System. According to the congenital syphilis surveillance case definition, congenital syphilis is 1) a condition affecting stillbirths and infants born to mothers with untreated or inadequately treated syphilis regardless of signs in the infant or 2) a condition affecting an infant with clinical evidence of congenital syphilis including direct detection of Treponema pallidum or a reactive nontreponemal syphilis test with signs on physical examination, radiographs, or cerebrospinal fluid analysis ( 3 ). Rates of congenital syphilis mirror rates of primary and secondary syphilis among women of reproductive age, which approximately doubled during 2014–2018 ( 3 ). Adequate maternal treatment is defined as completion of a penicillin-based regimen recommended for the mother’s stage of syphilis initiated ≥30 days before delivery ( 2 ). For this analysis, all congenital syphilis prevention opportunities are considered timely if they occurred ≥30 days before delivery, per the surveillance case definition ( 3 ). Demographic and clinical characteristics of infants and their mothers were analyzed using Stata statistical software (version 11; StataCorp). On the basis of CDC’s congenital syphilis prevention framework, each congenital syphilis case was assigned to one of four mutually exclusive missed opportunity categories based on the mother’s prenatal care, testing, and treatment history: 1) lack of timely prenatal care with no timely syphilis testing; 2) lack of timely syphilis testing despite timely prenatal care; 3) lack of adequate maternal treatment despite a timely syphilis diagnosis;* or 4) late identification of seroconversion during pregnancy (identified 41% of mothers of infants with congenital syphilis lacked timely prenatal care, and >29% lacked adequate treatment despite receipt of a timely syphilis diagnosis. TABLE 3 Missed congenital syphilis prevention opportunities among mothers of infants with congenital syphilis in the South and West U.S. Census regions,* by race/ethnicity † — United States, 2018 Missed prevention opportunity Census region and race/ethnicity No. (%§) South West White Black Hispanic White Black Hispanic No timely prenatal care and no timely syphilis testing 37 (31.6) 68 (19.7) 26 (13.0) 56 (43.1) 37 (43.0) 81 (41.8) No timely syphilis testing despite receipt of timely prenatal care 7 (6.0) 26 (7.5) 14 (7.0) 17 (13.1) 6 (7.0) 23 (11.9) No adequate maternal treatment despite a timely syphilis diagnosis 28 (23.9) 128 (37.0) 74 (37.0) 38 (29.2) 26 (30.2) 57 (29.4) Late identification of seroconversion during pregnancy¶ 18 (15.4) 34 (9.8) 19 (9.5) 7 (5.4) 4 (4.7) 14 (7.2) Missed prevention opportunity not identified Clinical evidence of congenital syphilis despite adequate maternal treatment completion** 5 (4.3) 17 (4.9) 9 (4.5) 3 (2.3) 2 (2.3) 2 (1.0) Insufficient information†† 22 (18.8) 73 (21.1) 58 (29.0) 9 (6.9) 11 (12.8) 17 (8.8) Total 117 346 200 130 86 194 * South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming. † White and black mothers were non-Hispanic; Hispanic mothers might be of any race. § Percentages might not sum to 100 because of rounding. ¶ Must have had negative syphilis test early in pregnancy and a positive syphilis test <30 days before delivery, at day of delivery, or ≤90 days after delivery to be classified as having a seroconversion during pregnancy. ** Infant indications of infection include direct detection of Treponema pallidum by dark field microscopy or special stains; a reactive nontreponemal test and any one of these signs or symptoms of congenital syphilis: condyloma lata, snuffles, syphilitic rash, hepatosplenomegaly, jaundice/hepatitis, pseudoparalysis, or edema on physical exam; long bone radiograph findings consistent with congenital syphilis; abnormal protein or white blood cell count in the cerebrospinal fluid; reactive venereal disease research laboratory test in the cerebrospinal fluid. †† Insufficient information submitted to CDC related to maternal prenatal care, testing, or treatment to categorize. Discussion Nationally, the most commonly missed opportunity for preventing congenital syphilis was lack of adequate maternal treatment, likely driven by the high numbers of cases in the South, where this missed opportunity was most prevalent. The most common missed opportunities for preventing congenital syphilis differed by geographic region. In the West, a lack of timely prenatal care was the most commonly missed opportunity, and in the Northeast, late identification of seroconversion was the most common. Regional clinical and demographic differences in mothers of infants with congenital syphilis indicate that different populations are at increased risk and might require different interventions. The high proportion of mothers with early syphilis in certain regions signals recent heterosexual transmission and the potential for future increases in congenital syphilis cases if no intervention occurs. The high proportions of symptomatic and stillborn infants in certain regions might be related to early syphilis among their mothers, given that higher rates of vertical transmission and worse infant outcomes are associated with early syphilis during pregnancy ( 5 ). Published analyses of state-level data demonstrate additional heterogeneity in prevalences of missed opportunities and priority interventions. Repeat syphilis testing early in the third trimester was recently identified as the main intervention for preventing congenital syphilis in Florida, Louisiana, and New York City ( 6 , 7 ). A review of recent congenital syphilis cases in Indiana found that social vulnerabilities, including homelessness, substance abuse, and incarceration, were barriers to receiving timely diagnosis and treatment, despite provider adherence to CDC guidelines ( 8 ). A California study of missed opportunities for prevention of congenital syphilis identified gaps in multiple steps of the prevention cascade and found that early prenatal care is critical to preventing congenital syphilis and that multifaceted efforts are needed ( 9 ). Establishment of congenital syphilis case review boards in Louisiana identified specific missed opportunities, including lack of screening and treatment delay ( 10 ). These data support the need for tailored interventions based on local epidemiology and analysis of missed prevention opportunities. A national congenital syphilis prevention strategy requires prioritizing interventions to address the root causes of missed opportunities while maximizing the impact of finite resources. Interventions are needed for identifying pregnant women with syphilis outside of prenatal care and for reducing barriers to prenatal care for all women. Ensuring timely follow-up of positive syphilis test results for pregnant women and reducing barriers to adequate syphilis treatment for pregnant women and their partners can prevent congenital syphilis cases. Syphilis screening for all pregnant women at the first prenatal visit with repeat screening at 28 weeks and at delivery for women in high prevalence areas or who are at increased risk for acquisition can further reduce congenital syphilis and its associated morbidity. These interventions require collaboration among public health authorities, health care organizations and providers, and policymakers. Jurisdictions can establish congenital syphilis case review boards that can identify local prevention failures and explore solutions. The differences in missed opportunities noted among regions and among racial/ethnic groups within regions demonstrate that tailored prevention efforts are needed. The findings in this report are subject to at least three limitations. First, U.S. jurisdictions have different processes for congenital syphilis case investigation and reporting, and congenital syphilis investigations can be time-consuming and complicated. Inaccurate or incomplete data can lead to misclassification of missed prevention opportunity categories and might have magnified observed regional differences. Second, case report data provide limited information regarding each infant with congenital syphilis and each mother of an infant with congenital syphilis; this can lead to underascertainment of such factors as seroconversion. Finally, national congenital syphilis case report data do not contain information regarding social determinants of health such as maternal substance use; thus, this analysis cannot address the multifactorial barriers to accessing prenatal care and receiving adequate treatment. Congenital syphilis prevention requires syphilis prevention for women and their sex partners and timely identification and treatment of pregnant women with syphilis. Improving access to prenatal care and family planning for all women can improve rates of congenital syphilis as well as many other maternal and child health outcomes. Regional differences in the missed prevention opportunities indicate a need for different priorities for interventions that address root causes of congenital syphilis. Halting the continued increases and eventually eliminating congenital syphilis in the United States will require collaboration between public health and health care sectors, understanding missed prevention opportunities, and implementing tailored interventions accordingly. Summary What is already known about this topic? Timely identification and treatment of maternal syphilis can prevent congenital syphilis; however, the number of congenital syphilis cases in the United States increased 261% during 2013–2018. What is added by this report? Nationally, the most commonly missed opportunities for prevention of congenital syphilis are a lack of adequate maternal treatment despite timely diagnoses of syphilis (31%) and a lack of timely prenatal care (28%), followed by late identification of seroconversions (11%); prevalences of these missed opportunities differ regionally and by race/ethnicity. What are the implications for public health practice? Halting continued increases in congenital syphilis requires understanding the missed prevention opportunities and implementing tailored interventions based on local experience.
Resumo: O Brasil tem registrado aumento nas incidências de sífilis gestacional e congênita, revelando-se como um importante problema de saúde pública no país. O trabalho teve como objetivo analisar a relação entre as ofertas de diagnóstico e tratamento da sífilis na atenção básica e as incidências de sífilis gestacional e congênita. Foi realizado estudo ecológico analisando as incidências desses agravos e a cobertura de ações diagnósticas e terapêuticas na atenção básica. A amostra do estudo foi composta por municípios com população acima de 20.000 habitantes, com cobertura da atenção básica superior a 50% e nos quais a maioria das equipes foi avaliada no segundo ciclo do Programa de Melhoria do Acesso e da Qualidade na Atenção Básica. Para analisar a efetividade das ações de detecção e tratamento foi desenvolvido o Índice de Variação da Transmissão Vertical de Sífilis. A administração da penicilina e a realização de teste rápido nesses municípios obtiveram medianas iguais a 41,9% e 67,14%, respectivamente, com diferenças regionais. A mediana da incidência de sífilis gestacional foi 6,24 (IIQ: 2,63-10,99) em municípios com maior oferta de teste rápido, e de 3,82 (IIQ: 0,00-8,21) naqueles com oferta inferior, apontando aumento na capacidade de detecção. Municípios com redução da transmissão vertical apresentavam maiores medianas dos percentuais de equipes com oferta dos testes rápidos (83,33%; IIQ: 50,00-100,00) e realização de penicilina (50,00%; IIQ: 11,10-87,50), demonstrando relação entre estas ações e a redução de sífilis congênita. Os achados indicam a necessidade de ampliação dessas ofertas e reforça a importância na redução da transmissão vertical.
Abstract Introduction Congenital syphilis cases in the United States increased 755% during 2012–2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment. Methods A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis. Results In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions. Conclusions and implications for public health practice Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.
AUTHOR CONTRIBUTIONS: Oliveira GG, Palmieri IGS and Lima LV collaborated with the study conception
and design, analysis and interpretation of the results, drafting and
critical reviewing of the manuscript content. Pavinati G, Santos VMA, Luz
KCSI and Magnabosco GT collaborated with data analysis and interpretation,
drafting and critical reviewing of the manuscript content. All authors have
approved the final version of the manuscript and declared themselves to be
responsible for all aspects of the work, including ensuring its accuracy and
integrity.
CONFLICTS OF INTEREST: The authors declare they have no conflicts of interest.
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