Use of Interrupted Time Series Analysis in Understanding the Course of the Congenital Syphilis Epidemic in Brazil

Use o In e up ed Time Se ies Analysis in Unde s anding he Cou se o he Congeni al Syphilis Epidemic in B azil Ra ael Pin o, a,b,c, *Rica do Valen im, a,b Ly ene Fe nandes da Sil a, a Gus a o Fon ou a de Souza, b,c Thaísa G ois Fa ias de Mou a San os Lima, b,d Ca los Albe o Pe ei a de Oli ei a, b,e Ma quiony Ma ques dos San os, a,b Ang elica Espinosa Mi anda, d, Alie e Cunha-Oli ei a, g,h Vi ekanandan Kuma , i and Ri a A un j a Fede al Uni e si y o Rio G ande do No e, Na al, RN, B azil b Labo a o y o Technological Inno a ion in Heal h (LAIS), Na al, RN, B azil c Fede al Ins i u e o Rio G ande do No e, Na al, RN, B azil d Minis y o Heal h, B asília, DF, B azil e S a e Uni e si y o Rio de Janei o, Rio de Janei o, RJ, B azil Fede al Uni e si y o Espí i o San o, ES, B azil g Heal h Sciences Resea ch Uni : Nu sing (UICISA: E) and Nu sing School o Coimb a (ESEn C), Coimb a, Po ugal h Cen e o In e disciplina y S udies o he 20 h Cen u y (CEIS20), Uni e si y o Coimb a, Coimb a, Po ugal i A habasca Uni e si y, A habasca, Canada j Ha a d School o Public Heal h, Ha a d Uni e si y, Bos on, MA, USA Summa y Backg ound To igh agains he ising incidence o syphilis, he B azilian Minis y o Heal h (MoH) launched he “Syphilis No!” P ojec (SNP), wi h speci ic esou ces unded by a pa liamen a y amendmen . Then, in 2018, a na ional apid esponse s a ed o be implemen ed on he B azilian Uni ied Heal h Sys em (SUS, Sis ema  Unico de Sa ude) in wo s a egic lines (1) o ein o ce SUS's uni e sal ac ions and (2) o implemen speci ic ones o 100 municipali ies chosen by he MoH as p io i ies o syphilis congeni al esponse. In 2015, such locali ies ep esen ed 6895% o congeni al syphilis cases in B azil. In his con ex , SNP has implemen ed ac ions o s eng hen epidemio- logical su eillance o acqui ed syphilis and congeni al syphilis by ins i u ing an in eg a ed and collabo a i e esponse h ough heal h se ices ne wo ks and ein o cing in e s a e ela ions. Me hods A quasi-expe imen al s udy using ime se ies analysis was conduc ed o assess immedia e impac s and changes o he end in na ional congeni al syphilis be o e and a e he p ojec , om Sep embe 2016 o Decembe 2019. Da a we e assessed conside ing a es o congeni al syphilis pe 1,000 li e bi hs in all p io i y municipali ies (n=100) co e ed by he p ojec and in non-p io i y municipali ies (n=5,470) om all i e mac o- egions o B azil. Findings P io i y municipali ies showed a g ea e educ ion (change in end) in compa ison o non-p io i y. The linea eg ession model e ealed end changes a e he in e en ion, wi h bo h g oups o municipali ies showing a d op in he a e age mon hly numbe o cases pe 1,000 li e bi hs, wi h a educ ion o -0¢21 (CI 95% -0¢33 o -0¢09; p=0¢0011) in p io i y municipali ies and o -0¢10 (CI 95% -0.19 o -0.02; p=0¢0216) in non-p io i y municipali ies. In e p e a ion The s udy using ITS p o ides impo an e idence on he di ec ion, iming, and magni ude o he e ec s o in e en ions in oduced as pa o he SNP on congeni al syphilis in B azil. Ou esul s sugges ha he Syphilis No! P ojec in luenced he ends o congeni al syphilis in B azil om 2018, wi h highe educ ions achie ed in he p io i y municipali ies. Funding The esea ch is unded by a g an o he Syphilis No! P ojec om B azilian Minis y o Heal h (P ojec Numbe : 54/2017). The unde s had no ole in s udy design, analysis, decision o publish, o p epa a ion o he man- usc ip . Copy igh Ó2021 The Au ho (s). Published by Else ie L d. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/) Keywo ds: public heal h; policy; in e up ed ime se ies; segmen ed eg ession analysis; no i iable disease; syphilis *Co esponding au ho . E-mail add ess: [email p o ec ed] (R. Pin o). The Lance Regional Heal h - Ame icas 2022;7: 100163 Published online 27 Decembe 2021 h ps://doi.o g/10.1016/j. lana.2021.100163 www. helance .com Vol 7 Mon h Ma ch, 2022 1 A icles In oduc ion Congeni al syphilis (mo he - o-child ansmission o e ical ansmission o syphilis o syphilis) causes dam- age o he e us i he mo he ’s in ec ion is no de ec ed and p ope ly ea ed du ing p egnancy. The Wo ld Heal h O ganiza ion (WHO) es ima es ha each yea 930,000 p egnan women ha e p obable ac i e syphilis wo ldwide each yea . I esul s in app oxima ely 350,000 ad e se bi h ou comes, including 143,000 ea ly e al dea hs/s illbi hs, 62,000 neona al dea hs, 44,000 p ema u e/low-bi hweigh babies, and 102,000 in ec ed in an s. 1,2 The Pan Ame ican Heal h O ganiza ion (PAHO) Membe S a es, suppo ed by WHO, in 2010 app o ed he S a egy and Plan o Ac ion o he Elimina ion o Mo he - o-Child T ansmission o HIV and Congeni al Syphilis. The s a egy was se o educe he incidence o congeni al syphilis o ≤0¢5 cases pe 1,000 li e bi hs by 2015. 3 None heless, B azil did no each he congeni- al syphilis elimina ion goal, which led a esu gence o acqui ed syphilis, syphilis in p egnan women and con- geni al syphilis ac oss he coun y. In 2010, 6,949 cases o congeni al syphilis we e epo ed o he B azilian Minis y o Heal h (2¢4/1,000 li e bi hs), whe eas, in 2015, his case coun inc eased o 19,647 (6¢5/1,000 li e bi hs) accoun ing o a g ow h a e o 170¢83%. 4 To igh he syphilis epidemic in B azil, in Oc obe o 2016, he Minis y o Heal h (MoH) issued he S a egic Ac ions Agenda o Reducing Syphilis in B azil. 5 This agenda es ablished a lis o p io i ies aimed in collabo a- ion wi h PAHO and o he ins i u ions such as uni e si- ies, in e na ional agencies, and s a e and municipal ep esen a i es. Fu he mo e, such agenda p omp ed a pa liamen a y amendmen wi h speci ic esou ces o implemen a na ional apid esponse in B azil’s Uni ied Heal h Sys em (SUS, Sis ema  Unico de Sa ude). The B azilian Minis y o Heal h in i ed s a e and municipal heal h manage s o igh syphilis h ough he “Syphilis No!” P ojec — ha included he “Applied Resea ch o In elligen In eg a ion Aimed a S eng h- ening Heal hca e Ne wo ks o Rapid Response o Syphilis”— o educe acqui ed syphilis, syphilis in p eg- nan women, and congeni al syphilis by expanding co - e age o diagnosis ( h ough apid es ing), and imely and p ope ea men o p egnan women and sexual pa ne s in p ena al ca e, childbi h, o abo ion si ua- ions. Th ough he P ojec , he syphilis epidemic has been aced up h ough wo s a egic lines: (1) ein o c- ing uni e sal ac ions o SUS and (2) implemen ing spe- ci ic ones o 100 municipali ies chosen by he MoH as p io i ies o syphilis congeni al esponse, as in 2015 hey ep esen ed 68¢95% o he numbe o congeni al syphilis cases in B azil. The uni e sal line o in e en ion included acqui ing and dis ibu ing es ing and ea men supplies (c ys al- line and benza hine penicillin), enhancing he STI labo- a o ies ne wo k and he si ua ion ooms o epidemiological su eillance, educommunica ion s a e- gies, 6 social in e en ions, and awa eness campaigns pe o med o ace syphilis in ha pe iod. A he same ime, ins i u ional suppo was g an ed o he p io i y municipali ies, whe e Resea ch and In e en ion Sup- po e s (RIS) ca ied ou speci ic wo k wi h local heal h manage s. Hence, his wo k p o ided echnical coope a- ion o s eng hen p e en ion ac ions aimed a educing he e ical ansmission o syphilis, such as imple- men ing commi ees ocused on in es iga ing syphilis Resea ch in Con ex E idence be o e his s udy We sea ched PubMed o a icles published up o Oc 1, 2021, using he e ms "syphilis" AND (" empo al analysis" OR " ime se ies" OR " eg ession me hods") AND "public heal h", wi h no language es ic ions. Ou sea ch iden i- fied six s udies. Fou o hem epo analysis o syphilis da a in B azil om a ime se ies pe spec i e, wi h di e - en se ings, showing he syphilis incidence a es inc eas- ing om 2007 o 2016 and he challenge o he B azilian Minis y o Heal h o educe he h ee o ms o syphilis (in p egnancy, congeni al and acqui ed). Apa om hese s udies, China epo ed ha syphilis incidence a es ha e inc eased h ee- old om 2005 o 2012 and ime se ies analysis was an e ec i e ool o modelling he his- o ical and u u e incidence. Added alue o his s udy We used in e up ed ime se ies o examine ends be o e and a e he in oduc ion o a public in e en- ion p ojec in B azil in o de o educe acqui ed syphilis, syphilis in p egnan women, and congeni al syphilis by expanding co e age o diagnosis ( h ough apid es - ing), and imely and app op ia e ea men o p egnan women and sexual pa ne s in p ena al ca e, childbi h, o abo ion si ua ions. Da a we e assessed conside ing a es o congeni al syphilis pe 1,000 li e bi hs in all p i- o i y municipali ies (n=100) co e ed by he p ojec and in non-p io i y municipali ies (n=5,470) om all fi e mac o- egions o B azil. Ou in e up ed ime se ies da a indica e changes in ends owa ds educ ion o s abiliza ion in almos all egions (No h, No heas , Sou h, and Sou heas ). This e ec may be a ibu ed o he p ojec 's uni e sal ac ions, ha is, gene al in e en ions ha we e designed and implemen ed in all B azilian s a es and municipali ies. Implica ion o all he a ailable e idence In ecen yea s (2010-2019) i is he fi s ime we can see a change in he cou se o congeni al syphilis in B azil. The e ec s o he in e en ion a he na ional le el e eals s a is ically significan end changes in mon hly a es o congeni al syphilis in B azil and shows a e a - ia ions by egion. A icles 2 www. helance .com Vol 7 Mon h Ma ch, 2022 cases and ein o cing local planning o esponse on he p ojec 's axis, among o he s. The de ails o he p ojec in e en ions and ele an imelines a e p esen ed in Appendix (Figu es A1 o A5). The pu pose o his s udy is o use in e up ed ime se ies o es ima e in e en ion e ec s o e ime by com- pa ing a es o congeni al syphilis pe 1,000 li e bi hs in he p io i y municipali ies (n=100) co e ed by he Syphilis No! P ojec and in non-p io i y municipali ies (n=5,470) in he i e mac o- egions o B azil: No h, No heas , Sou h, Sou heas , and Midwes . Me hods Conside ing ha a andomized con olled ial (RCT) is in easible o be pe o med in his s udy, we used a quasi-expe imen al esea ch design wi h in e up ed ime se ies (ITS) analysis. Such design enables compa i- sons in popula ion heal h ou comes be o e, du ing and a e an in e en ion wi hin a clea ly de ined span. 7 ITS is a good app oach o e alua ing longi udinal e ec s o heal h in e en ions. 8,9 Besides, i can be used as a s a- is ical me hod o es ima ing in e en ion e ec s o a policy change on an ou come o in e es . 10 The ITS design and he use o segmen ed eg ession analysis enables e alua ion o immedia e impac and slope asso- cia ed wi h a policy in e en ion while con olling he o e all end in he a e o he ou come o in e es . 10 This s udy was pe o med h ough a mul idimen- sional, lexible, and adap i e amewo k aimed a disco - e y and empo al analysis o public heal h in e en ions. I was implemen ed using he He mes sys em, 11,12 which manages a comple e da a li e cycle 13 by 1) acqui - ing da a om se e al ex e nal sou ces in di e en o - ma s; 2) cleaning da a o s anda diza ion and e o emo al; 3) ans o ming i in o speci ic models; 4) pub- lishing a dashboa d; 5) p ese ing da a as a s uc u ed da abase. Use o da a sou ces The He mes sys em was used o collec congeni al syph- ilis da a om he No i iable Diseases In o ma ion Sys- em (SINAN, Sis ema de In o ma¸c~ ao de Ag a os de No i ica¸c~ ao), p o ided by he B azilian MoH. These da a ep esen he o al numbe o no i ied cases pe munici- pali y, gi en by mon h and yea . The i al eco ds o li e bi hs by municipali y o each yea , we e e ie ed om he Heal h In o ma ics Depa men o he B azil- ian Minis y o Heal h (DATASUS) and used calcula e mon hly a e age li e pe municipali y pe yea . He mes de i ed he a es o congeni al syphilis cases by di iding mon hly cases pe municipali y by li e bi hs. P io i y s non-p io i y municipali ies B azil has 5,570 municipali ies sp ead o e i e mac o- egions—No h, No heas , Sou h, Sou heas and Midwes . Mon hly a es pe municipali y we e used o ca ego ise municipali ies in o p io i y and non-p io i y. The MoH classi ied he p ojec as a ool wi h wo lines o inducing esponse on syphilis: uni e sal and speci ic ac ions. Thus, p io i y municipali ies (n=100) we e de ined on popula ion and epidemiological c i e- ia, namely: he 27 capi als, in addi ion o municipali ies in me opoli an egions wi h mo e han 100,000 inhab- i an s ha had, in 2015, he highes a es o bo h con- geni al syphilis incidence in child en unde one yea o age and pe ina al mo ali y. The p io i y municipali ies ep esen ed 68¢95% o he o al congeni al syphilis cases in B azil. O he municipali ies (n=5,470) we e ca - ego ised as non-p io i y. Appendix (Figu e A6) p o ides geog aphic, demog aphic and socio-economic cha ac e - is ics o he i e egions and p esen s he geog aphic loca ion o 100 p io i y and 5,470 non-p io i y munici- pali ies. The p io i y municipali ies ecei ed suppo and echnical coope a ion om he p ojec 's ne wo k o Resea ch and In e en ion Suppo e s. Thei wo k ocused on he municipali ies'needs wi hin he axis o he p ojec , as i was moni o ed h ough he “LUES” pla o m, 14 made a ailable by he p ojec . The suppo - e s en e ed on he “LUES” pla o m all o hei echnical coope a ion ac i i ies o heal h eams and local manag- e s o p io i y municipali ies on a mon hly basis o sup- po ing ac ions o p e en mo he - o-child ansmission (MTCT) o syphilis. S a is ical analysis A quasi-expe imen al design was applied o analyze he ime se ies da a using a segmen ed linea eg ession model in he R so wa e, adap ed o exchange da a wi h He mes in o de o assess he immedia e impac and change in end o na ional congeni al syphilis a es p e and pos he SNP in e en ion. Wha is mo e, May o 2018 was conside ed he in e en ion s a ime poin o implemen ing he Syphilis No! P ojec . Appendix p o ides R code used in his analysis. Da a mus be collec ed egula ly o e ime and a equally spaced in e als o pe o m a segmen ed eg es- sion analysis. 9,15 To a oid any bias ela ed o he Co id- 19 pandemic, Decembe o 2019 was de ined as he end da e o he da a collec ion, o aling 20 mon hs p e- in e en ion (Sep/2016 o Ap /2018) and 20 mon hs pos -in e en ion (May/2018 o Dec/2019). A linea ela ionship be ween ime and he ou come wi hin each segmen was assumed, conside ing seg- men ed eg ession models i a leas squa es eg ession line o each segmen o he independen a iable ( ime), p<0¢05 was conside ed s a is ically signi ican . Thus, he nex s ep in he analysis was o es ima e he magni ude o he in e en ion and es he s a is ical sig- ni icance o immedia e impac and end a es. A icles www. helance .com Vol 7 Mon h Ma ch, 2022 3 The eg ession model used o i hese da a is s aigh o wa d. ou come =b 0 +b 1 * + b 2 * p io i y +b 3 * p io i y *i+b 4 * pos -in e en ion +b 5 *( -T I ) * pos -in e en ion +b 6 * pos -in e en ion * p io i y +b 7 * pos -in e en ion * * p io i y +e Whe e b 0 is he baseline ou come o he non-p io - i y g oup; b 1 is he p e-exis ing end in he ou come o in e es o he p io i y non-g oup; b 2 is he baseline di - e ence be ween non-p io i y and p io i y g oups; b 3 is he di e ence in end be ween non-p io i y and p io i y g oup be o e in e en ion; b 4 is he immedia e impac in he p io i y g oup; b 5 is he end change in he p io - i y g oup; b 6 is he di e ence in he immedia e impac change be ween he non-p io i y and p io i y a e in e - en ion, and b 7 is he di e ence in end change be ween he non-p io i y and p io i y g oup a e in e - en ion. P io i y a iable is coded 1 o p io i y and 0 o non-p io i y. The a iable is only an inc emen ha coun s up om 1 o 40 o e he en i e pe iod. The pos - in e en ion a iable was se o be 0 be o e he in e en- ion and 1 a e . T I is cons an ha ep esen s he in e - en ion momen , in his case is equal o 20. Figu e 1 ep esen s he model, including he immedia e impac and end change. O dina y Leas Squa es (OLS) eg ession analysis assumes ha e o e ms associa ed wi h each obse a- ion a e unco ela ed. Co ec ly inspec ing au oco ela- ion e ms can a oid unde es ima ed s anda d e o s and o e es ima ed signi icance o he e ec s o an in e - en ion. 15 In he case o his s udy, a Du bin-Wa son es was used o in es iga e he p esence o au oco ela- ion, in addi ion o esidual plo s, Au o Co ela ion Func ion (ACF) plo s, and pa ial-ACF plo s. Au oco e- la ion was no de ec ed in he s a is ical es s. R-squa ed is a s a is ical measu e o how close he da a a e o he i ed eg ession line. I is also known as he coe - icien o de e mina ion o he coe icien o mul iple de e - mina ion o mul iple eg ession. I was used in his esea ch’s model o de e mine how close he da a a e o he model and how i is p esen ed in he esul s. R-squa ed is a alue be ween 0 and 1, whe e 0 indica es ha he model explains none o he a iabili y o he esponse da a a ound i s mean, and 1 indica es ha he model explains all he a iabili y o he esponse da a a ound i s mean. Ou lie s a e ex eme alues ha do no seem o i in he ime se ies. I he ou lie e lec s an an icipa o y o sho - e m his o y e ec , he da a poin can be explici ly modeled. Al e na i ely, i he ou lie is an unambiguous clea consequence o he in e en ion, i can be ea ed as a egula da a poin o e alua e i s impac . A p elimi- na y analysis was pe o med, and a single ou lie was iden i ied in he Midwes egion a e he in e en ion (July 2018). The Mo ing A e age (MA) me hod was used o smoo h he da a o he pu pose o explaining empo al ends. The MA used was o o de h ee, which p o ides only a smoo hing wi h he wo mon hs (be o e and a e ) he calcula ed obse a ion. A e his p ocess, no ou lie emained. The eg ession models ob ained o each g oup (p i- o i y and non-p io i y municipali ies), using da a om he p e- and pos -in e en ion pe iods (May 2018), we e compa ed wi h he coun e ac ual o he pos -in e en- ion pe iod conside ing he end obse ed be o e he in e en ion. The coun e ac ual enables a compa ison be ween he obse ed change and wha would ha e hap- pened had he in e en ion no aken place. The eg es- sion model pa ame e s we e ob ained by poin and in e al es ima ion using 95% o con idence. Figu e 1. In e up ed ime-se ies pa ame e ized as a segmen ed eg ession model, including he immedia e impac and end change. The solid lines ep esen he obse ed alues, and do ed lines indica e he coun e ac ual o he pos -in e en ion pe iod. A icles 4 www. helance .com Vol 7 Mon h Ma ch, 2022 Role o he unding sou ce The unde s had no ole in s udy design, da a collec ion, da a analysis, in e p e a ion, decision o publish, o p epa a ion o he manusc ip . Resul s Resul s o he ime se ies analysis compa ing a es o congeni al syphilis pe 1,000 li e bi hs in he p io i y municipali ies and non-p io i y municipali ies a e p e- sen ed in Table 1 and Figu es 2 o 7. The ed do s ep e- sen he mon hly a es o cases in p io i y municipali ies and he blue do s in non-p io i y ones. The con inuous lines indica e he eg ession models ob ained o each g oup (p io i y and non-p io i y), using da a om he p e- and pos -in e en ion pe iods (May 2018). Mo eo e , he do ed lines indica e he coun e ac ual o he pos -in e en ion pe iod using he da a end obse ed be o e he in e en ion. Table 2 p esen s his compa ison conside ing he las mon h o he analyzed pe iod (20 h mon h, Decembe o 2019). These esul s desc ibe he in e en ion e ec s in de ail o each egion, sepa a ely. Tha is because i cap- u es he egionalized in luence o he Uni ied Heal h Sys em go e nance—which is in e ede a i e, wi h clea a ibu ions a local, s a e, and ede al le els. In his sense, as P ima y Heal h Ca e (PHC) is a esponsibili y o municipali ies, e idence ha he SNP e ec s can a y ac oss egions can be cap u ed. Fo he No h egion o B azil, in Figu e 2 and Table 1 (column 2), o bo h p io i y and non-p io i y municipali- ies, he e was a educ ion in he mon hly a e o congeni- al syphilis cases in he pos -in e en ion pe iod. The mon hly a e age educ ion was -1¢77 cases pe 1,000 li e bi hs in p io i y municipali ies and -009 pe 1,000 li e bi hs in non-p io i y municipali ies, as shown in Table 1. In addi ion, he es ima ed linea eg ession models o each si ua ion show changes in he mon hly a e age ends, wi h a -0¢05 educ ion in he p io i y municipali ies and a -0¢07 educ ion o he non-p io i y ones. The coun e ac ual p esen ed in Table 2 shows ha o he p io i y municipali ies he model es ima ed 18¢08 cases pe 1,000 li e bi hs a he end o he 20 h mon h wi hou in e en ion. In compa ison, wi h in e - en ion, 13¢73 cases we e obse ed o he same ime poin , indica ing a decline o 24¢09%. In he non-p io - i y municipali ies, he model es ima ed 5¢11 mon hly cases pe 1,000 li e bi hs in he 20 h mon h. The obse ed alue wi h he in e en ion was 3¢63 pe 1,000 li e bi hs, which ep esen s a all o 28¢97%. Figu e 3 and Table 1 (column 3) display he esul s o he No heas egion, whe e an inc easing o 2¢23 cases pe 1,000 li e bi hs in immedia e impac can be obse ed pos -in e en ion in p io i y loca ions. The e was also a 0¢34 educ ion in cases o non-p io i y municipali ies. A change in end can be obse ed o bo h g oups. Non-p i- o i y municipali ies e e sed he upwa d end wi h a mon hly slope o -0¢11 cases pe 1,000 li e bi hs. Mean- while, p io i y municipali ies showed a slope o -0¢64 cases pe housand li e bi hs pos in e en ion. Rega ding he coun e ac ual (Table 2) o his egion, a he end o he span analyzed in p io i y municipali ies and wi hou in e en ion, he model es i- ma ed 28¢11 cases pe 1,000 li e bi hs, compa ed o 15¢75 cases obse ed a e in e en ion (a d op o 43¢95% o his g oup). In non-p io i y municipali ies, he model es ima ed 5¢33 cases in he las mon h o da a collec ion, while he ac ual alue wi h he in e en ion was 3¢63 pe 1,000 li e bi hs, a decline o 31¢79%. As ep esen ed in Figu e 4 and Table 1 (column 4), p io i y municipali ies in he Sou h egion showed a sha p d op o -1¢76 mon hly cases pe 1,000 li e bi hs, and a end change o -0¢28 mon hly cases pe 1,000 li e bi hs. Con e sely, in he non-p io i y municipali- ies he e was an inc ease o 0¢48 in mon hly cases pe 1,000 li e bi hs and a mino end change o -0¢04 mon hly cases pe 1,000 li e bi hs. The model es ima ed 26¢13 cases pe 1,000 li e bi hs i no in e en ion had aken place in he p io i y municipali ies om he Sou h egion. The ac ual alue wi h in e en ion, was 18¢42 cases pe 1,000 li e bi hs, ep esen ing a decline o 29¢48%. A sligh dec ease o 4¢27% was obse ed o non-p io i y municipali ies wi h an es ima ed 5¢82 coun e ac ual cases and 5¢57 ac ual cases pe 1,000 li e bi hs. The non-p io i y municipali ies in he Sou heas egion (Figu e 5 and Table 1, column 5) wen h ough an inc ease o 0¢13 mon hly cases pe 1,000 li e bi hs and a change in end wi h a dec ease o -0¢16 mon hly cases. Whe eas he p io i y municipali ies expe ienced a -1¢11 educ ion in mon hly cases and sligh ly declining end o -0¢02 mon hly cases. The coun e ac ual o his egion p ojec ed an es i- ma ed 20¢84 cases pe 1,000 li e bi hs in p io i y munici- pali ies (Table 2) in he absence o in e en ion. Howe e , a educ ion o 21¢21% o 16¢42 cases pe 1,000 li e bi hs was obse ed. In he Sou heas egions’s non-p io i y municipali ies, he coun e ac ual was 8¢70 cases agains 5¢85 ac ual cases pe 1,000 li e bi hs, wi h a 32¢69% educ ionin hepos -in e en ionpe iod. In he Midwes egion (Figu e 6 and Table 1, column 6), he e was a educ ion o -0¢47 mon hly cases in he p io i y municipali ies ollowing he in e en ions, bu an inc ease o 0¢87 mon hly cases in he non-p io i y municipali ies. The e was a e e sal o he end in he p io i y municipali ies om 0¢09 mon hly cases pe 1,000 li e bi hs p e-in e en ion o -0¢07 pos in e en- ions. Con e sely, in non-p io i y loca ions, he e was a e e sal o he end in he opposi e di ec ion. In his manne , a downwa d end o -0¢02 mon hly cases be o e in e en ion changed o 0¢00 in he pos -in e - en ion pe iod. The coun e ac ual o he pos -in e en ion pe iod in p io i y municipali ies was 12¢52 cases pe 1,000 li e www. helance .com Vol 7 Mon h Ma ch, 2022 5 A icles No h No heas Sou h Sou heas Midwes B azil alue (CI 95%) p- alue alue (CI 95%) p- alue alue (CI 95%) p- alue alue (CI 95%) p- alue alue (CI 95%) p- alue alue (CI 95%) p- alue P e-In e en ion In e cep 1¢45 (0¢71 o 2¢19) <0¢001 2¢45 (1¢51 o 3¢39) <0¢001 4¢65 (3¢49 o 5¢82) <0¢001 4¢45 (3¢61 o 5¢30) <0¢001 2¢54 (1¢71 o 3¢37) <0¢001 3¢44 (2¢71 o 4¢17) <0¢001 Di e en ial be ween g oups 11¢39 (10¢35 o 12¢44) <0¢001 15¢58 (14¢25 o 16¢91) <0¢001 15¢04 (13¢39 o 16¢68) <0¢001 8¢38 (7¢18 o 9¢58) <0¢001 6¢87 (5¢70 o 8¢04) <0¢001 10¢96 (9¢92 o 12¢00) <0¢001 T end in p io i y g oup 0¢04 (-0¢05 o 0¢13) 0¢393 0¢18 (0¢07 o 0¢29) 0¢002 0¢13 (-0¢01 o 0¢27) 0¢062 0¢09 (-0¢01 o 0¢19) 0¢077 0¢09 (-0¢01 o 0¢19) 0¢063 0¢11 (0¢03 o 0¢20) 0¢011 T end in non-p io - i y g oup 0¢09 (0¢03 o 0¢16) 0¢004 0¢07 (0¢00 o 0¢15) 0¢062 0¢03 (-0¢07 o 0¢13) 0¢539 0¢11 (0¢04 o 0¢18) 0¢003 -0¢02 (-0¢08 o 0¢05) 0¢665 0¢08 (0¢01 o 0¢14) 0¢017 Pos -In e en ion Immedia e impac in p io i y g oup -1¢77 (-3¢20 o -0¢34) 0¢016 2¢23 (0¢42 o 4¢05) 0¢016 -1¢76 (-4¢00 o 0¢49) 0¢123 -1¢11 (-2¢75 o 0¢53) 0¢181 -0¢47 (-2¢07 o 1¢13) 0¢560 -0¢36 (-1¢77 o 1¢06) 0¢618 Immedia e impac in non-p io i y g oup -0¢09 (-1¢10 o 0¢92) 0¢865 0¢34 (-0¢94 o 1¢62) 0¢598 0¢48 (-1¢11 o 2¢07) 0¢548 0¢13 (-1¢03 o 1¢29) 0¢822 0¢87 (-0¢26 o 2¢00) 0¢131 0¢28 (-0¢72 o 1¢28) 0¢583 Change in end in p io i y g oup -0¢05 (-0¢18 o 0¢07) 0¢407 -0¢64 (-0¢80 o -0¢48) <0¢001 -0¢28 (-0¢48 o -0¢09) 0¢005 -0¢02 (-0¢16 o 0¢13) 0¢827 -0¢07 (-0¢21 o 0¢06) 0¢291 -0¢21 (-0¢33 o -0¢09) 0¢001 Change in end in non-p io i y g oup -0¢07 (-0¢16 o 0¢01) 0¢099 -0¢11 (-0¢22 o 0¢00) 0¢058 -0¢04 (-0¢18 o 0¢10) 0¢579 -0¢16 (-0¢26 o -0¢06) 0¢003 0¢00 (-0¢09 o 0¢10) 0¢949 -0¢10 (-0¢19 o -0¢02) 0¢021 R 2 0¢9816 0¢9877 0¢9767 0¢9691 0¢9590 0¢9848 Table 1: Resul s o he ime se ies analysis compa ing a es o congeni al syphilis pe 1,000 li e bi hs be ween p io i y and non-p io i y municipali ies. 6 www. helance .com Vol 7 Mon h Ma ch, 2022 A icles bi hs a he end o he pe iod (Table 2), compa ed o 16¢42 ac ual cases, which ep esen s a all o 21¢21%. By con as , he compa ison be ween he coun e ac ual (1¢94) and ac ual (2¢86) cases pe 1,000 li e bi hs o he non-p io i y municipali ies e ealed a 47¢86% inc ease. The combined analysis o he na ional da a e eals a decline in he immedia e impac o congeni al syphilis pos -in e en ion, wi h an a e age mon hly educ ion o -0¢36 cases pe 1,000 li e bi hs in he p io i y munici- pali ies. Con e sely, he e was an inc ease o 0¢28 cases pe 1,000 li e bi hs in non-p io i y municipali ies. In he linea eg ession model, examina ion o he ends o bo h g oups ollowing he in e en ion, e eals a dec ease in he g ow h o he a e age numbe o cases pe 1,000 li e bi hs. Hence, he e was a educ ion o -0¢21 in p io i y municipali ies and o -0¢10 in non-p io - i y ones, as depic ed in Figu e 7 and Table 1 (column 7). Figu e 2. Changes in congeni al syphilis a es in he No h egion 20 mon hs be o e and a e he in e en ion. Figu e 3. Changes in congeni al syphilis a es in he No heas egion 20 mon hs be o e and a e he in e en ion. www. helance .com Vol 7 Mon h Ma ch, 2022 7 A icles Fo p io i y municipali ies, he combined analysis also indica es a educ ion o 28¢79% in he numbe o cases in he las mon h o he analyzed pe iod (Table 2) when compa ed he coun e ac ual o 21¢93 wi h he ac ual numbe o 15¢61 cases pe 1,000 li e bi hs. In he non-p io i y municipali ies, he e was a d op o 26¢20%. Acco dingly, i wen om 6¢34 coun e ac ual cases o 4¢68 ac ual cases pe 1,000 li e bi hs. As o congeni al syphilis in p io i y and non-p i- o i y municipali ies, he mos ema kable di e en- ces we e ound in he No heas (15¢58 pe 1,000 li e bi hs) and Sou h (15¢04 pe 1,000 li e bi hs) egions, ollowed by he No h (11¢39 cases pe 1,000 li e bi hs), Sou heas (8¢38 cases pe 1,000 li e bi hs) and Midwes (6¢87 cases pe 1,000 li e bi hs). Figu e 4. Changes in congeni al syphilis a es in he Sou h egion 20 mon hs be o e and a e he in e en ion. Figu e 5. Changes in congeni al syphilis a es in he Sou heas egion 20 mon hs be o e and a e he in e en ion. 8 www. helance .com Vol 7 Mon h Ma ch, 2022 A icles Discussion The indings indica e a s a is ically signi ican educ ion in he end o congeni al syphilis cases in B azil in he 20 mon hs ollowing he Syphilis No! P ojec in e en ions. Addi ionally, he esul s e eal ha p io i y municipali ies expe ienced a mo e signi ican educ ion in congeni al syphilis cases when compa ed o o he B azilian munici- pali ies wi h a g ea e educ ion in he end. Fo p io i y municipali ies, he p ojec ’s impac on changing he cou se o congeni al syphilis ends was mo e e iden . Unlike he o he ou B azilian egions, he mos signi ican change in he g ow h end was obse ed in he No heas , which showed a sha p d op. Fu he mo e, dec easing pos -in e en ion ends we e obse ed in he No heas and Sou h egions. Mean- while, he e was s abiliza ion o he end in he No h. Figu e 6. Changes in congeni al syphilis a es in he Midwes egion 20 mon hs be o e and a e he in e en ion. Figu e 7. Changes in congeni al syphilis a es in B azil 20 mon hs be o e and a e he in e en ion. www. helance .com Vol 7 Mon h Ma ch, 2022 9 A icles