Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population

Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population

International Journal of Infectious Diseases 39 (2015) 10–15 Contents lists available at ScienceDirect International Journal of Infectious Diseases ...

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International Journal of Infectious Diseases 39 (2015) 10–15

Contents lists available at ScienceDirect

International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid

Prevalence of syphilis, human immunodeficiency virus, hepatitis B virus, and human T-lymphotropic virus infections and coinfections during prenatal screening in an urban Northeastern Brazilian population Adriana Avila Moura a,*, Maria Ju´lia Gonc¸alves de Mello b,c, Jailson B. Correia b,d a

Universidade Federal de Alagoas, Maceio´, Brazil Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil c Faculdade Pernambucana de Sau´de, Recife, Brazil d Universidade de Pernambuco, Recife, Brazil b

A R T I C L E I N F O

Article history: Received 16 June 2015 Received in revised form 18 July 2015 Accepted 25 July 2015 Corresponding Editor: Eskild Petersen, Aarhus, Denmark. Keywords: Seroepidemiologic studies Prenatal diagnosis STDs Coinfection

S U M M A R Y

Objectives: To evaluate prevalences of Treponema pallidum, human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), and hepatitis B virus (HBV) infections and coinfections during prenatal screening in an urban Northeastern Brazilian population through a large dataset. Methods: Secondary data were obtained from the Maceio´ (Alagoas, Brazil) municipal prenatal screening program from June 2007 to May 2012. Dried blood serum tests from 54,813 pregnant women were examined to determine prevalences of T. pallidum, HIV, HTLV, and HBV infections and coinfections, and the seroconversion rates for syphilis and HIV infection. Socio-demographic variables associated with syphilis and HIV infection were identified. Results: The prevalences of syphilis, HIV, HTLV, and HBV infections were 2.8%, 0.3%, 0.2%, and 0.4%, respectively. Pregnant women infected with T. pallidum had a 4.62-fold greater risk of HIV coinfection, and pregnant women infected with HIV had a 5.71-fold greater risk of T. pallidum coinfection. Seroconversion for syphilis and HIV during pregnancy occurred in 0.5% and 0.06% of women, respectively. Among the women carrying HTLV, 4.2% also had an HBV infection. Conclusions: Syphilis was twice as prevalent among pregnant women in Maceio´, compared to the national average, and coinfections with syphilis/HIV and HTLV/HBV were significantly associated among these pregnant women. ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

1. Introduction Early diagnosis and proper management during pregnancy and after childbirth can reduce mother-to-child transmission of syphilis, the human immunodeficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), and the hepatitis B virus (HBV).1,2 Approximately 1.5 million pregnant women worldwide are infected with Treponema pallidum annually; if untreated, 50% of them will experience adverse events, including stillbirth, prematurity, and deaths.3 Furthermore, in 2006, the World Health

* Corresponding author. Universidade Federal de Alagoas, Av. A´lvaro Otacı´lio, 6491/603, Jatiu´ca, Maceio´/AL, Brazil. Tel.: +558299026148. E-mail address: [email protected] (A.A. Moura).

Organization reported that 2.3% of pregnant women tested positive for HIV infections in low-and middle-income countries.4 Thus, the elimination of mother-to-child transmission of HIV and syphilis have been incorporated into the World Health Organization’s Millennium Development Goals 4, 5, and 6.5 To achieve these goals, prenatal screening is critical to preventing mother-to-child transmission via interventions during pregnancy, childbirth, and the post-partum period.4,5 An estimated 240 million individuals worldwide are infected with HBV, with a male:female distribution ratio of approximately 1.5:1.6 Based on these statistics, we can assume that there are approximately 90 million female carriers of HBV, many of whom are of childbearing age. Their babies can also become chronic carriers of the HBV s-antigen (HBsAg) if they do not receive preventative treatment.7 In addition, these individuals have a

http://dx.doi.org/10.1016/j.ijid.2015.07.022 1201-9712/ß 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A.A. Moura et al. / International Journal of Infectious Diseases 39 (2015) 10–15

greater risk of developing hepatocellular carcinoma.8 Therefore, the identification of pregnant women who are carriers of HBsAg is an important strategy for preventing mother-to-child transmission.7 An estimated 15–20 million people worldwide are infected with HTLV-1 or HTLV-2,8 and mother-to-child transmission typically occurs during breastfeeding.8 There are no national data regarding the number of pregnant women who are carriers of HTLV in Brazil, and the Ministry of Health does not currently recommend prenatal screening for HTLV.9 However, because they have common transmission routes, increases in the prevalences of syphilis and infection with HIV, HTLV, and HBV can overlap. In addition, their magnitude and vulnerability to preventive methods during pregnancy makes them global public health concerns (albeit to differing degrees).10 Therefore, we conducted this large study to determine the prevalences of syphilis and HIV, HTLV, and HBV infections and coinfections during prenatal screening among pregnant women in an urban Northeastern Brazilian population. In addition, we evaluated the seroconversion rates of syphilis and HIV infection, and evaluated the association between various sociodemographic variables and syphilis or HIV infection. 2. Materials and methods This study used a descriptive, observational, cross-sectional design to evaluate data from the Maceio´ antenatal infectious diseases screening registry. The Maceio´ Municipal Health Office authorized the use of these data (July 2012) and the ethics committee of the Instituto de Medicina Integral Prof. Fernando Figueira approved the study design (CAAE: 06733812.2.0000.5201; Plataforma Brasil). 2.1. Population, prenatal testing, data collection, and processing Maceio´, the capital of the State of Alagoas, is located in northeastern Brazil and had 76,862 births between June 2007 and May 2012.11 Based on an average miscarriage rate of 16% in northeastern Brazil,12 it was estimated that 89,159 pregnancies occurred in Maceio´ during this period. Approximately 74.7% of the population are public healthcare users,13 which indicates that more than 66,600 of the pregnant mothers received public healthcare. Between June 2007 and May 2012, 54,813 pregnant women who sought treatment at the Maceio´ Universal Healthcare System ´ nico de Sau´de, SUS) were screened for T. pallidum, HIV, (Sistema U HTLV, and HBV infections during their first prenatal care visit. The Municipal Health Office antenatal disease screening program screened 61.4% of all pregnancies in the municipality, and 82.3% of pregnancies that received prenatal care via the public healthcare system during this period. The evaluation form for the included women recorded their date of birth, self-reported ethnicity, number of abortions, gestational age at the first prenatal visit, and district of residence, based on the 7 health districts in Maceio´. Those health districts are defined using common geographic characteristics, and have significant urban social inequalities.14 The screening program consisted of collecting capillary blood samples via S&S #903 filter paper (Schleicher & Schuell, Keene, NH) for serological testing at the laboratory of the Instituto de Pesquisa e Diagno´stico Laboratorial of the Association of Parents and Friends of Handicapped Children of Maceio´ (Associac¸a˜o de Pais e Amigos dos Excepcionais: APAE Maceio´). In this laboratory, the blood samples were re-suspended for enzyme-linked immunosorbent assay (ELISA) testing for anti-T. pallidum antibodies, antiHTLV antibodies, HBsAg, anti-HBc antibodies, and anti-HIV antibodies, according to the manufacturer’s specifications. The specific kits were the Q-Preven Total Syphilis-DBS, Q-Preven HIV

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1+2-DBS, Q-Preven HTLV-1+2-DBS, and Q-Preven HBsAg-DBS, which are manufactured by Symbiosis Diagno´stica Ltd (Sa˜o Paulo, Brazil). When a woman tested positive for any of these tests, a second peripheral blood sample was collected and analyzed via conventional testing at the same laboratory to confirm the preliminary findings. Pregnant women were considered to be infected with T. pallidum based on the Venereal Disease Research Laboratory (VDRL) test (any titer), with HIV based on ELISA and western blot (WB) anti-HIV testing, with HTLV-1 and -2 based on ELISA and WB anti-HTLV-1 and -2 testing, and with HBV based on anti-HBc and HBsAg ELISA testing. Only pregnant women who underwent the entire diagnostic procedure for each disease were included in our analyses. During the third trimester, capillary blood was collected again to screen for syphilis and HIV infection, using the same criteria (Figure 1). 2.2. Data analysis Statistical analyses were performed using Stata software (version 12.1, StataCorp LP, College Station, TX, USA), and differences with a p-value of <0.05 were considered statistically significant. The analyzed variables included the prevalences of syphilis, HIV, HTLV, and HBV infections, and the seroconversion rates for syphilis and HIV infections. The prevalences of syphilis and HIV infection were tested for associations with age group (19 years old or >19 years old), self-reported ethnicity (mixed race, white, black, or Asian), number of miscarriages (<2 or 2), beginning of prenatal care (<12 weeks of gestation or 12 or more weeks of gestation), and the district of residence (Maceio´ health district 1–7). Differences between proportional data were compared using the chi-square test, and variables with a p-value of 0.20 in the univariate analyses were included in the multivariate model. 3. Results Among 54,813 pregnant women who provided capillary blood samples during their first trimester, 54,744 (99.9%) were tested for syphilis, 54,811 (99.9%) were tested for HIV infection, 54,798 (99.9%) were tested for HTLV infection, and 54,798 (99.9%) were tested for HBV infection. The birth date was reported by 99.6% of the participants, ethnicity by 92.6%, beginning of prenatal care by 85.1%, number of abortions by 75.3%, and district of residence by 85.1%. The average age was 23.3  6.1 years (95% confidence interval [CI]: 15–35 years), and 31.5% of the participants were adolescents (19 years old). Pregnant women self-reported their ethnicity as mixed race (68.3%), white (21.8%), black (8.8%), or Asian (1%). Gestational age at the beginning of prenatal care was 16.4  7 weeks (95% CI: 8–30 weeks), and 34% of the participants began their prenatal care at 12 weeks of gestation. Table 1 lists the prevalences of syphilis, HIV, HTLV, and HBV infections according to the participants’ socio-demographic and antenatal characteristics. Table 2 lists the general prevalences of syphilis, HIV, HTLV, and HBV infections. Among the pregnant women who were seronegative for syphilis or for HIV during their first trimester, 42% and 43% were tested again during their third trimester, respectively. Seroconversion for syphilis was observed in 123 (0.5%) of these participants and seroconversion for HIV occurred in 14 (0.06%) of these participants. Syphilis was more prevalent among women who were >19 years old, compared to among adolescents (adjusted odds ratio [aOR]: 1.87; p < 0.001), although age was not significantly associated with HIV prevalence. Syphilis and HIV infections were more prevalent among self-reported non-white women, compared to white women (aORs: 1.63 and 1.26, respectively; p < 0.05). Syphilis was more prevalent among women who began prenatal

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A.A. Moura et al. / International Journal of Infectious Diseases 39 (2015) 10–15

Figure 1. Flowchart for the Municipal Health of Maceio´ prenatal screening program during the study period.

care after 12 weeks of gestation and among women who had 2 miscarriages (aORs: 1.21 and 1.87, respectively; both p < 0.01), although there was no significant association with the prevalence of HIV infection. Syphilis was more prevalent among pregnant women from Maceio´ health districts 2 and 5 (aORs: 1.92 and 1.40 respectively; both p < 0.05), although there were no districtspecific differences in the prevalences of HIV infection (Tables 3 and 4). The overall prevalence of coinfection was 0.08%, and the proportions of coinfections are listed in Tables 5 and 6. Pregnant women who were infected with T. pallidum had a 4.62-fold greater risk of being coinfected with HIV (p < 0.001), and pregnant women who were infected with HIV had a 5.71-fold greater risk of being coinfected with T. pallidum (p < 0.001) (Tables 3 and 4). Among pregnant women with syphilis, 3 (0.5%) seroconverted to HIV during pregnancy (p < 0.001), and the rate ratio for HIV seroconversion among these women was 11.02-fold greater than that among women who did not have syphilis (p < 0.001). One woman who was infected with HIV seroconverted to syphilis during pregnancy, and another seroconverted to both HIV and

syphilis during pregnancy. However, HIV and HTLV coinfection was not observed in the study population. 4. Discussion The present study’s findings revealed a syphilis prevalence of 2.8% among pregnant women who underwent prenatal care at public healthcare facilities in a Northeastern Brazilian capital city, which is 2.3-fold greater than the prevalence from a national study (1.20%).15 However, methodological differences in the diagnostic testing may have contributed to this discrepancy. Disparate prevalences have been reported in various regions of Brazil, which indicates a heterogeneous distribution of syphilis.16,17 We also observed a 0.5% seroconversion rate for syphilis during the third trimester in Maceio´, which is similar to the reported national rates.15 Therefore, it is important to perform continued surveillance and counseling of pregnant women during all prenatal care visits, and to provide treatment for the women and their partners. In Brazil, the prevalence of HIV infection among pregnant women is 0.4%,18 although several studies have reported regional

A.A. Moura et al. / International Journal of Infectious Diseases 39 (2015) 10–15 Table 1 Prevalence of syphilis, HIV infection, HTLV infection and HBV infection according to socio-demographic and antenatal characteristics of urban pregnant Northeastern Brazilian women (2007?2012). Syphilis % (screened)

HIV infection % (screened)

Age (years) 19 1.4 (17,220) 0.3 (17,231) >19 3.5 (37,329) 0.4 (37,385) <0.0001 0.1 p-value* Ethnicity White 2.3 (11,090) 0.2 (11,108) Non-white 3.0 (39,604) 0.4 (39,651) p-value* <0.0001 0.014 Beginning of Prenatal care (weeks) 12 2.3 (15,807) 0.3 (15,827) 3.0 (30,763) 0.4 (30,805) >12 p-value* <0.0001 0.052 Miscarriage <2 2.5 (38,649) 0.3 (38,692) >2 7.0 (2,546) 0.5 (2,559) p-value* <0.0001 0.13 District of residence 1st district 2.2 (4,533) 0.4 (4,539) 2nd district 4.0 (7,580) 0.4 (7,598) 3rd district 2.6 (3,882) 0.3 (3,885) 4th district 2.3 (5,418) 0.2 (5,425) 5th district 3.0 (10,028) 0.3 (10,035) 6th district 2.7 (8,152) 0.5 (8,163) 7th district 2.6 (13,093) 0.3 (13,107) p-value* <0.001 0.065

HTLV infection % (screened)

HBV infection % (screened)

0.2 (17,229) 0.2 (37,374) 0.299

0.3 (17,225) 0.4 (37,378) 0.062

0.2 (11,105) 0.2 (39,642) 0.566

0.4 (11,107) 0.4 (39,641) 0.384

0.2 (15,822) 0.2 (30,796) 0.24

0.4 (15,823) 0.4 (30,798) 0.179

0.2 (38,682) 0.4 (2,557) 0.039

0.4 (38,684) 0.6 (2,557) 0.262

0.2 (4,539) 0.4 (7,957) 0.1 (3,884) 0.3 (5,423) 0.2 (10,033) 0.3 (8,162) 0.2 (13,131) 0.012

0.4 (4,540) 0.5 (7,596) 0.4 (3,885) 0.3 (5,422) 0.3 (10,033) 0.5 (8,158) 0.4 (13,105) 0.528

HIV: human immunodeficiency virus, HTLV: human T-lymphotropic virus, HBV: hepatitis B virus.

variations from 0.16% to 0.6%.19–21 In this study, we found a 0.3% seroprevalence of HIV infection among pregnant women, and a 0.06% seroconversion rate during pregnancy. This seroconversion rate occurred in a population with approximately 50% coverage

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during the second test, compared to 15% coverage during the second test in the national study.18 These findings reaffirm the consensus that pregnant women should be screened for HIV infection, and support the recommendation of a HIV second test during the third semester or delivery, in order to provide effective interventions that can prevent mother-to-child transmission.1,22 Only ethnicity was associated with HIV infection in our multivariate analysis. This higher HIV infection prevalence among nonwhite women is likely due to a lower socioeconomic status, which is more common among non-white women in Brazil.23 Syphilis and HIV coinfection occurred in 0.05% of the pregnant women in Maceio´, and our multivariate analysis revealed a strong risk of HIV-infected pregnant women becoming coinfected with T. pallidum (aOR: 5.71; p < 0.001). Among pregnant women who had HIV infection, 15.1% were coinfected with syphilis, which is approximately 5.5-fold higher than the national study rate (2.85%; aOR: 4.75).18 Syphilis facilitates HIV infection in several ways, and coinfection can promote the aggravation and progression of both diseases.24 We found an HTLV seroprevalence of 0.2% among the screened pregnant women. Other Brazilian studies have reported seroprevalences among pregnant women that range from 0.1% to 1.05%.21,25 Prenatal screening for HTLV-1 and -2 infections is not recommended in populations with a low seroprevalence, despite there being no available treatment, and the transmission rate is estimated at 2.7% for non-breastfed infants.2 Therefore, local seroprevalence studies should be performed to identify at-risk groups during prenatal care, and this information should be used to guide policy decisions regarding screening pregnant women for HTLV. The prevalence of HBV infection among pregnant women was 0.4% in Maceio´. Previous studies have reported similar prevalences of 0.3–0.8% among pregnant Brazilian women.19,26 The administration of the HBV vaccine and HBV-specific immunoglobulin within 12 h of birth increases the efficacy of the prophylactic

Table 2 Prevalence of syphilis, and HIV, HTLV, and HBV infections and seroconversion rates for syphilis and HIV infection among urban pregnant Northeastern Brazilian women (2007–2012).

Syphilis HIV infection HTLV infection HBV infection

Screened

Prevalence (95% CI)

Second test (n)

Seroconversion rate (95% CI)

54,744 54,811 54,798 54,798

2.8 0.3 0.2 0.4

23,003 23,549 -

0.5 (0.45–0.64) 0.06 (0.03–0.10) -

(2.69–2.97) (0.29–0.39) (0.18–0.26) (0.36–0.47)

HIV: human immunodeficiency virus, HTLV: human T-lymphotropic virus, HBV: hepatitis B virus, CI: confidence interval.

Table 3 Univariate and multivariate analysis of socio-demographic factors that were associated with syphilis among urban pregnant Northeastern Brazilian women (2007–2012). Multivariate analysisa

Univariate analysis

Age >19 years Non-white 2 miscarriages Beginning of prenatal care (>12 weeks of gestational age) District of residence 1st district 2nd district 3rd district 4th district 5th district 6th district 7th district HIV infection

OR

95% CI

p

OR

95% CI

p

2.55 1.33 2.92 1.29

2.22–2.92 1.17–1.53 2.48–3.45 1.14–1.46

0.001 0.001 0.001 0.001

1.87 1.26 1.87 1.21

1.53–2.28 1.06–1.50 1.54–2.27 1.05–1.41

0.001 0.009 0.001 0.009

0.001 1.00 1.83 1.20 1.02 1.36 1.24 1.17 6.17

1.42–2.30 0.95–1.58 0.78–1.33 1.09–1.72 0.99–1.58 0.93–1.47 4.12–9.25

0.001 0.209 0.878 0.007 0.070 0.170 0.001

0.001 1.92 1.39 1.02 1.40 1.34 1.22 4.62

1.44–2.64 0.95–1.97 0.71–1.49 1.03–1.89 0.97–1.83 0.90–1.64 2.72–7.84

0.001 0.069 0.899 0.031 0.073 0.199 0.001

a The final model was adjusted for age group, ethnicity, miscarriages, beginning of prenatal care, district of residence and HIV infection. HIV: human immunodeficiency virus, OR: odds ratio, CI: confidence interval.

A.A. Moura et al. / International Journal of Infectious Diseases 39 (2015) 10–15

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Table 4 Univariate and multivariate analysis of socio-demographic factors that were associated with HIV infection among urban pregnant Northeastern Brazilian women (2007– 2012) Univariate analysis

Age >19 years Non-white 2 miscarriages Beginning of prenatal care (>12 weeks of gestational age) District of residence 1st district 2nd district 3rd district 4th district 5th district 6th district 7th district Syphilis a

Multivariate analysis

OR

95% CI

p

1.31 1.69 1.55 1.41

0.95–1.83 1.11–2.59 0.87–2.75 0.99–2.00

0.101 0.015 0.133 0.050

1.22 1.45 1.07 0.70 1.00 1.70 1.00 6.17

0.68–2.18 0.91–2.33 0.56–2.04 0.36–1.37 0.61–1.62 1.08–2.64

0.073 0.511 0.119 0.848 0.296 0.990 0.020

4.12–9.25

0.001

OR

95% CI

p

1.63

1.05–2.54

0.030

5.71

3.75–8.69

0.001

The final model was adjusted for ethnicity and Treponema pallidum infection. HIV: human immunodeficiency virus, OR: odds ratio, CI: confidence interval.

program from 72% (through routine vaccination alone) to 97%.7,27 Therefore, routine screening of pregnant women remains important in countries where the vaccine is administered, as the diagnosis of HBV infection can help guide the healthcare team in administering immunoglobulin to the newborn. In our data, we infrequently observed cases of coinfection with syphilis and HBV, syphilis and HTLV, or HBV and HIV; no cases of HIV and HTLV were reported. HBV and HTLV coinfection occurred in 0.009% of the participants, and although rare, this association was statistically significant. Among pregnant women who were infected with HTLV, 4.2% were also carriers of HBV (p < 0.001). We have found no other studies that have evaluated this association among pregnant women. Our multivariate analysis revealed that syphilis was associated with age (>19 years old), and this increased prevalence among older women may be related to successive reinfection. Non-white pregnant women had a higher prevalence of syphilis, which is Table 5 Prevalences of coinfections among urban pregnant Northeastern Brazilian women (2007–2012). Coinfection

Screened

%

Syphilis

HIV HTLV HBV

54,742 54,729 54,729

0.050 0.007 0.009

HIV

HBV HTLV

54,796 54,729

0.002 0

HTLV

HBV

54,783

0.009

HIV: human immunodeficiency virus, HTLV: human T-lymphotropic virus, HBV: hepatitis B virus. Table 6 Proportion of coinfections with syphilis, HIV, HTLV, and hepatitis B among urban pregnant Northeastern Brazilian women (2007–2012). Coinfections (%) Syphilis

n Syphilis p-value HIV infection p-value HTLV infection p-value Hepatitis B p-value a

a

1,550 186 118 226

15.1 <0.001 3.4a 0.688 2.2 0.581

HIV 1.8 <0.001 0 0.4b 0.786

HTLV 0.3 0.688 0 2.2 <0.001

Hepatitis B 0.3 0.581 0.5 0.786 4.2 <0.001 -

Baseline = 116; b baseline = 225. HIV: human immunodeficiency virus, HTLV: human T-lymphotropic virus, HBV: hepatitis B virus.

similar to the national report’s findings.15 We also found an association between syphilis and late initiation of prenatal care, which is considered an independent risk factor for high-risk pregnancies, and may indicate reduced access to health services, low education level, or lack of interest or knowledge regarding the importance of early pregnancy monitoring.28 In this study, syphilis was associated with the number of abortions (2). Unfortunately, miscarriages and perinatal or neonatal deaths occur in 40% of children who are infected via untreated mothers,29 which may also indicate that these pregnant women are long-time carriers of the disease. Maceio´ health districts 2 and 5 also had significantly higher syphilis prevalences. Lower income and lower education, compared to other health districts, may explain those findings.14 Nevertheless, it is possible that non-assessed factors may also be responsible for the higher prevalences in those districts. Therefore, studies are needed to deepen our understanding of these communities’ characteristics and to define local public health strategies that can modify the prevalence of syphilis. In conclusion, our findings support continuous screening of pregnant women for syphilis, HIV, and HBV infection, especially given the severity of syphilis and HIV coinfection. While our assessment of associated factors is limited by the small number of variables that were collected during the routine screening program, this study concomitantly evaluated 4 infectious diseases and their coinfections, and determined the seroconversion rates of two diseases that have high priority in public healthcare. Furthermore, few other studies have reported the coinfection rates of infectious diseases among pregnant women. Therefore, as Maceio´ has urban characteristics and social, economic, and health service structures that are similar to other medium-sized Northeastern Brazilian urban centers, our findings may be relevant to promote systematic screening of pregnant women in these centers, and to support appropriate public policies and prevention strategies to improve individual and societal health. Conflicts of interest: None. Source of support: DECIT/SCTIE/MS from the National Council of Technological and Scientific Development (CNPq); Fundac¸a˜o de Amparo a` Pesquisa de Alagoas (FAPEAL); Secretaria de Estado da Sau´de de Alagoas (SESAU-AL). The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Author contribution: AAM conceived the idea, participated in the data collection, in the literature review, and in writing and reviewing the manuscript. MJGM supervised the study and revised the manuscript.

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JBC supervised the study and reviewed the manuscript All authors have approved the final article. Ethics statement: The ethics committee of the Instituto de Medicina Integral Prof. Fernando Figueira approved the study design (CAAE: 06733812.2.0000.5201; Plataforma Brasil).

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