Inpiiscad bireme bviegi-bin/vilexelscad/ BRI0803360 E-Mail: artigos.fps@gmail.com Pedido:080508-169 Usuario: Semin Perinatol 1998 22(4) pags. 323-31 / Hollier LM; Cox SM / Syphilis. [(iah) MEDLINE_1997-2008 pmid: 9738997) | Fonte de referéncia:{iah) MEDLINE_1997-2008 pia! | 9738997 Associacao Pele Saudavel ‘Av Arnolfo Azevedo 160 Pacaembu (1236-030 - So Paulo - SP BRASIL BRIO803360 E-Mail artigos fps@amaiicom VINA AACA A Semin Perinatol Pedido:080508-169 1998 22(4) pags. 323-31 / Hollier LM; Cox SM / Syphilis. (ah) MEDLINE_1997-2008 pid: 9738997) ““*Possui acesso eletronico™* Local: BR1.1 Opgées: BR1.1 / BR66.1/BR18.1 ——4 Atendido / Paginas: [ 7 Rejeitado / Motive: 145 / 156Syphilis Lisa M. Hollier and Susan M. Cox Syphilis was first recognized as a distinct syndrome in Europe in the fifteenth century. Despite Knowledge of congenital infection for more than 450 years and the existence of adequate therapy for 55 years, congenital infection remains a problem for the practicing clinician. Syphilis is caused by Treponema pallidum. Infection may be transmitted horizontally by sexual contact and vertically as a ‘result of hematogenous dissemination across the placenta. Syphilis is classified as primary, secondary, latent, and tertiary. The diagnosis may be established by darkfield examination of clinical lesions and by serological assays. The drug of choice for syphilis is penicillin. This agent is the only antibiotic of proven value for the treatment of congenital syphilis. Accordingly, infected pregnant women who are allergic to beta-lactam antibiotics must be desensitized and then treated with penicillin. Copyright © 1998 by W.B. Saunders Company Sei sega afer direct contact with ulcerative, denuded lesions of the skin or mucous membranes of infected persons. Sexual contact is the most common method of hori- zontal transmission. The mean incubation pe- riod for acquired primary syphilis is about 3 ‘weeks but may range from 10 to 90 days. ‘There was a dramatic increase in syphilis cases among young women in the late 1980s and early 1990s. The crack cocaine epidemic and the ex: ‘change of sex for drugs were important contribu tors t0 this resurgence, In 199, more than 45% of the total reported cases of primary and sec ondary syphilis occurred in southeastern states that constitute only 19% of the total US popula- tion.' The majority of cases occurred in New York, California, Florida, Texas, and Michigan. ‘The past several years have seen a decrease in primary and secondary syphilis cases among women in the United States. The reason for this recent downward wend remains unclear. Cer tainly, the awareness of the syphilis epidemic has led to wider screening practices and identifica- tion of infected persons. More recently, the wend also has been attributed to a combination ‘of community-based approaches that identify particular communities with a high prevalence Of syphilis and core populations at high risk for infection ‘The dramatic increase in the number of cases ‘of congenital syphilis that occurred in the late 1980s and early 1990s was caused by an increase in actual cases as well as the adoption in 1989 of revised reporting guidelines that broadened the surveillance definition for congenital syphilis. Previous criteria for reporting cases of congeni- tal syphilis were based on a clinical case defini- tion (Kaufinan criteria). The incidence of con- genital syphilis over the last several years has fallen, paralleling the decreasing incidence of primary and secondary syphilis in women. Vertical Transmission and Pathogenesis ‘The etiologic agent of syphilis is Treponema pal. Jidum, a spirochete approximately 10 to 12 jm in length. Its coo narrow to be seen by conventional light microscopy, It has a glycosoaminogiycan layer that_may have antiphagocytic capacity, three- sheathed flagellae at each end, six major proteins in the outer membrane, and a double wall that ‘contains cardiolipins, some of which may be incor- porated from damaged host tissues” Both treponemal and nontreponemal anti- bodies are formed in response to the infection, ‘These antibodies, however, do not arrest the pro- gression of the disease nor are they protective. ‘An individual with congenitally acquired disease can later acquire syphilis from horizontal trans- mission, The specific antibodies formed are of both the IgG and IgM class and are usually pres cent by the time the primary lesion appears. If the patient remains untreated, both classes will persist, After treatment, however, the IgM class disappears, whereas the IgG persists for life.” ‘rom he University of Teas Southern Mei Gtr a Datos, Dalles, TX. Adds erin ret to Lisa M. Holi, MD, Unies of Texas Southoetrn Metical Contr et Dells, 9323 Hay Hines Bod Daas, TX 73235 9032. Copyright © 1998 by W.B. Sunes Company 19146 0005/98/22040011$08.00/0 Seminars im Perinatology, Vol 22, No 4 (August), 1998: pp 325381 323324. Holler and Cox ‘The cervical changes of hyperemia, eversion, and friability that occur during pregnancy may facilitate the entry of T pallidum and lead to maternal spirochetemia.’ Syphilitic pregnant ‘women may transmit the infection to their fe- tuses at any clinical stage of the disease, but the highest transmission occurs in untreated. preg- nant women with primary syphilis. Congenital syphilis usually results from the transplacental infection of the developing fetus. Spirochetes have been detected in fetal tissue from spontane- ous abortions at 9 to 10 weeks’ gestation.® Na than etal’ have demonstrated spirochetes in am- niotic fluid as early as 14 weeks gestation proving that 7 pallidum can gain access to the fetal com- partment early in gestation.° Transmission is also possible during delivery by contact of the new- born with a genital lesion. Several studies have assessed the risk factors for delivery of an infant with congenital syphil Tnadequacy of prenatal care,’ use of cocaine,” degree of elevation of the Venereal Disease Re- search Laboratory (VDRL) titer,” and advanced gestational age at treatment® were all found to be risks. Clinical Presentation ‘The primary stage of syphilis is characterized by a painless chancre with local adenopathy. ‘The lesion develops at the site of inoculation about 3 weeks after exposure but may take up t0 90 days to appear. It begins asa painless papule and progresses to a red, round, firm ulcer with a ‘granular base and raised! edges. Adenopathy is ‘ypically mobile and nontender without suppura- tion. Most commonly, chaneres occur on the la- bia or fourchette; however, cervical chaneres may oceur. Other atypical locations include the tongue and areola of the breast. The chancre heals spontaneously in 8 10 8 weeks with little scarring, Nearly all patients with untreated infection will progress to secondary syphilis within 4 to 10 weeks, Widespread hematogenous and lym- phatic dissemination of T pallidum is characteris tic of this stage. Clinical findings include fever, malaise, sore throat, headache, adenopathy, and cutaneous or mucosal rash, The rash is diffuse, bilateral, and symmetric. The typical skin lesions are round and hyperpigmented, measuring 0.5, to 2 cm in size with distinct borders. The genital lesions are condylomata lata and mucous patches, The condylomata latum is a raised, white-gray papule often found on the labia. Dis- crete lesions are nontender and may coalesce. ‘Mucous patches are superficial, erosive lesions of the labia minora, Both types of genital lesions have a high concentration of spirochetes that can be detected with darkfield microscopy. Le- sions typically resolve in 3 to 12 weeks Latent syphilis is the period of infection in which serological test results for syphilis are posi- tive, but no clinical manifestations are present. The two subcategories of latent syphilis are earty latent with duration of infection of less than 1 year and late latent, when infection has been pres- cent for greater than 1 year. Mucocutancous le- sions may recur in approximately 25% of pa- tients with early latent disease.” Perinatal and sexual transmission of syphilis remains signifi- cant during this period of early latency. Trans- mission rates for late latent infections are much lower. Tertiary syphilis develops in approximately ‘one third of individuals after longstanding, un- treated infection. Manifestations include benign gummatous syphilis, cardiovascular syphilis, and neurosyphilis. The benign granulomatous gum- mas develop in 15% of patients." Cardiovascu- lar syphilis, characterized by aorttis, develops in at least 10% of untreated patients.!"? Neuro syphilis, manifested by meningovascular disease, paresis, and tabes dorsalis, develops in 7%."°!2" Pregnancy Pregnaney has no known effect on the clinical course of syphilis. It can, however, complicate or delay the diagnosis. False-positive results to the nontreponemal screening tests have been associ ated with pregnancy.” The majority of women diagnosed with syphilis during pregnancy have latent infection—30% early latent and 40% late latent in one study. An additional 22% had sec- ondary syphilis, and 8% had primary disease.” Syphilis, however, has a profound effect on the pregnancy. Untreated syphilis can result in spontaneous abortion, stillbirth, nonimmune hydrops, premature delivery, and perinatal death."***" In the years 1988 to 1995, syphilis accounted for over 6% of the stillbirths at Park- land Memorial Hospital.” In several African na- tions, rates of stillbirth from syphilis range from 5% to 42%." The frequency of delivery at lessGestational and Congenital Syphilis 325, than 37 weeks is two to four times higher in women with untreated syphilis." Birth weights are also significantly less in untreated patients, compared with treated and uninfected pa tients." Congenital Syphilis Rates of congenital infection vary by the clinical stage of maternal infection. Approximately 50% of infants born to women with untreated primary or secondary syphilis will be clinically affected at birth,"* whereas neonatal infection will develop in the remainder. Forty percent of gravidas with carly latent infection and 6% to 14% of those with late latent infection will deliver a congeni- tally infected infant Congenital infection with T' pallidum is di- vided into two syndromes by the time of presen- tation of clinical manifestations. When symp- toms appear within the first 2 years of life, the disease is termed early congenital syphilis. Symp- toms occurring after that time and often mani- fested near puberty, constitute late congenital “phils, Early Manifestations ‘The appearance of infected neonates is highly variable, with as many as 66% of infants ap- pearing normal at birth and other infants se verely hydropic.” In newborns who initially are asymptomatic, symptoms usually begin to appear by the third to the eighth week of life. The signs and symptoms of congenital syphilis are a conse- quence of active infection with T paidum and the resultant inflammatory response induced in various body organs and tissues. The most char acteristic abnormalities are hepatosplenoma- galy, erythematous maculopapular rash, and bone lesions. The rash is most prominent on the hands and feet. Abnormalities of the bones may be one of the ‘earliest findings, occurring as the only manifesta- tion in approximately 20% of infants." Lesions ‘occur most often in the long bones, especially the humerus and femur and are bilateral and symmetric. The classic radiograph shows a “moth-eaten” appearance to the bone with a thickened periosteum in reaction to the in- flammatory changes in the diaphysis. Another classic presentation of early congeni- tal syphilis is the nasal discharge, “‘snutffles.” It ‘Table 1. Cli Congenital 1 Findings in Infants With Karly pills Nonimmune hydrops Intrauterine growth restietion Reticuloendothelial abnormalities “Jaundice Hepatitis Hepatosplenomegaly ‘Anemia ‘Thrombocytopenia Adenopathy Mucocutaneous lesions Rhinitis (snes) Skin rash Mucous patch, Condylomata lata Bone abnormalities Periostits Osteachondritis cular abnormalities Choriozetinitis Cataract Glaucoma/uvettis Gontral nervous system abnormalities ‘Acute leptomeningitis Chronic meningovasculitis Hydrocephalus ‘Cfanial nerve palsies Cerebral infarction Seiaures Hypopituitarism ‘Rdapoed and reprinted wih permission ™ generally occurs within the first week of life, but may be delayed for 2 to 8 months. The involve- ment of the nasal mucosa may be extensive, and the discharge is teeming with spirochetes. Other manifestations of early congenital syphilis are listed in Table 1 Late Manifestations ‘The stigmata of late congenital syphilis represent scars induced by the initial lesions of early con- genital syphilis or reactions to persistent in- flammation.”7 Hutchinson's iad, which is virtu- ally pathognomonic for congenital syphilis, consists of Hutchinson's teeth, interstitial kerati- tis, and eighth-nerve deafness. Interstitial kerati- tis is the most common late lesion. Other late findings are listed in Table 2 Diagnosi Maternal The diagnosis of syphilis can be established by identification of the pathogen, T pallidumin clin-326 Hollior and Cox ‘Table 2. Signs of Late Congenital Syphilis ‘Newrolagical Abnormalities ‘Sheetal Abnormalities Dental Abnormalities Mental retardation Bighth cranial nerve deafness Hydrocephalus Saddle nose Frontal bossing Short mandible Peg:shaped upper incisors Mulberry molars Perioral fissures (rhagades) Protruding mandible Higharched p: Saber shins Fi ing scapulas Bilateral knee effusions ‘lapted and reprinted wih pennision.™ ical specimens when patients are infected with primary or secondary syphilis. Darkfield exami nation can be performed on material taken from ‘a moist genital lesion or a regional lymph node. Improved yield can be obtained by gently abrad- ing the lesion before pressing a glass slide against it. Injection of 0.5 ml. of normal saline followed by aspiration of the regional node may yield or ganisms, Nontreponemal serological test results at this time may be negative in cases of recent primary infection. Screening is accomplished by nontreponemal tests such as the Venereal Disease Research Lab- oratory (VDRL) or the Rapid Plasma Reagin (RPR) tests. The antigen used in these tests is composed of lecithin, cholesterol, and purified cardiolipin (diphosphotidylglycerol), which is a ‘component of mammalian cell membranes, to detect an antibody against cardiolipin that is present in the sera of patients with syphilis. These test results are reported as negative or as positive with titers; higher titers are associated with active disease. Titers are highest with sec. ‘ondary syphilis, somewhat lower with primary, and lowest with latent infection. The nontrepo- nemal test results become positive approxi- mately 4 to 8 weeks after infection™ and are thus reactive in only 80% of patients with primary “syphilis” In contrast, they are reactive in almost all patients with secondary and early latent syphi- lis. False-positive results can be obtained with other infections (Epstein-Barr virus),°°°" nar cotic and intravenous drugs abuse,” and various autoimmune diseases.” When a positive result is obtained with a non- treponemal test, a specific test for antitrepone- mal antibodies should be performed.”*** These are most commonly the Microhemaglutination Assay for Antibodies to Treponema pallidum (MHA-TP) or the Fluorescent Treponemal Anti- body-Absorption (FTA-ABS) test. These test re- sults are simply reported as positive or negative. In infected adults these test results remain posi tive indefinitely. The FTA-ABS is the more sensi tive of the two for the diagnosis of primary syphi- lis, although 18% of adults can be seronegative with primary infection." The MHATP is less sensitive, with up to 36% of individuals with pri mary syphilis testing negative.” For other stages of spphilis, the two tests are relatively equivalent, Because the MHACTP is less expensive and re {quires fewer resources, it has essentially replaced. the FTA-ABS for the follow-up of positive non- ‘reponemal testing. Patients with a history of treated infection may bbe serofast. Such patients are often identified by a low titer nontreponemal result and a positive weponemalspecific test despite appropriate therapy. We recommend followup on these ‘women with monthly RPR or VDRL- assays during, pregnancy. Reinfection in the serofast patient is diagnosed if a fourfold rise in tter occurs. The same type of nontreponemal test should be used! to make the diagnosis because of the differences in measured titers between RPR and VDRL. Because of the tremendous morbidity associ- ated with congenital infection, screening of all pregnant women has been shown to be cost ef fective even in populations of low prevalence." ‘The CDC recommends serological screening for syphilis at the first prenatal visit, in the third trimester, and again at delivery in high-tisk pop- ulations.” Prenatal Diagnosis Prenatal diagnosis of fetal syphilis is possible by the use of ultrasonography, which can identify' | 1 | I i | | | Gestational and Congenital Syphilis 327 hydrops fetalis in the presence of maternal syphi- lis" The other sonographic findings associ- ated with fetal syphilis are hepatosplenomegaly land placentomegaly. Satin et al" also found di- Jated small bowel and hepatomegaly in a fetus ‘who was subsequently stillborn to a mother with early latent syphilis Involvement of the amnionic cavity has been demonstrated by several methods, Rabbit infec- tivity testing (RIT) has been used to confirm the presence of 1'palldwm in amniotic fluid. Nathan et al” correlated detection of spirochetes by a positive RIT with fetal hepatomegaly measured sonographically. Additionally, 7 pallidum has also been detected in the amniotic fluid using PCR. A sensitivity of 91% and a specificity of 100% (compared with RIT) was achieved with this technique. Detection of fetal involvement is possible using cordocentesis. Fetal IgM specific for the lipoproteins of T' pallidum has been de- tected in fetal blood obtained at 24 weeks." This fetus also had anemia, thrombocytopenia, and ‘elevated liver enzymes, Congenital Syphilis ‘The new guidelines for the diagnosis of congeni tal syphilis were established in 1989 and are out- lined in Table 8.” This new definition includes all infants with clinical evidence of active syphilis as well as asymptomatic infants and stillbirths bor to women with untreated or inadequately treated syphilis. The diagnosis can be established by detection of spirochetes in suspicious lesions, body fluids, oF Ussues by dark-field microscopy, silver staining or immunofluorescence, or by polymerase chain reaction for T pallidum DNA. Detection of spirochetes represents the only means of confirming a congenital infection, If congenital infeetion is suspected, the placenta (ith the umbilical cord) should be sent for eval: uation. Microscopic evaluation of the placenta will often show the triad of enlarged hypercellu- Jar villi, proliferative fetal vascular changes, and acute or chronic villiis.* Spirochetes can also be detected in tissues from stillborn infants." Radiographic evaluation of long bones can dem- onstrate osteochondritis, even in markedly mac- ‘erated stillborns."* Because of the difficulties inherent in the demonstration of spirochetes, serological testing is most frequently used for diagnosis. As with adults either the RPR or the VDRL. can be used in infants, It is recommended that the same test be used for both che mother and the newborn to facilitate comparisons between titer results. Becatise of the possibility of umbilical cord blood contamination by maternal blood at the time of delivery, the CDC recommends using infant serum for determination of infection.” When evaluating the infant's titer, it is important to remember that it reflects not only the infants status, but also the transplacental passage of ma- ternal IgG. A presumptive diagnosis of congeni- tal syphilis can be made when the infant's titer is fourfold higher than that found in maternal serum.” Maternal IgM does not cross the pla- centa; therefore, detection of FTA-ABS-19S1gM antibody in the newborn serum provides pre- sumptive evidence of congenital infection. ‘Any infant bora to a seropositive mother should have a complete examination to rule out ‘evidence of congenital syphilis. In addition to the serological testing, a lumbar puncture is nec- essary to evahiate the CSF for cell count, protein, and VDRL. Long bone radiographs are recom- mended, and other tests, including complete blood count and liver function evaluation, should be performed as clinically indicated.” ‘Treatment Maternal Therapy Despite more than 50 years of use, penicillin remains the drug of choice for the treatment of syphilis, Infected pregnant women should be tested for other sexually transmitted diseases, particularly human immunodeficiency virus (HIV) infection. They then should be given the regimen appropriate for their clinical stage of infection (Table 4). Therapeutic failure does ‘occur, In a study of 340 women treated for syphi- lis during pregnancy, six did not respond to ther apy. The majority of those not responding (67%) ‘were women who had secondary syphilis—a stage associated with a high degree of spirochet- ‘emia and widespread dissemination."* For this reason, we recommend a second dose of ben- zathine penicillin G 1 week after the initial dose. Currently, there are no randomized trials com- paring the efficacy of one versus two injections. Other failures occur when the mother is treated within the last 4 weeks of pregnancy."** One pos- sible explanation for this is altered penicillin| | | 328. Holler and Cox ‘Table 3. Surveillance Case Definition for Congenital Syphilis Confirmed ‘Any infant with identification of T pallidum by darkfield microscopy, fluorescent antibody, fF other specific stains in specimens from lesions, placenta, umbilical cord, or autopsy material Presumptive ny infant whose mother has untreated or inadequately treated syphilis at delivery oR Any infant with a positive teponemal test for syphilis PLUS one of the following: Evidence of congenital syphilis on examination including long-bone radiographs Reactive CSF VDRL. Elevated! CSF white blood eell count or protein (without other cause) ‘Quantitative titers of nontreponemal serology ‘that are fourfold higher than maternal tess (both drawn at birth) Reactive test for FTA-ABS-19S1gM antibody Syphiliiesillbirts ‘A feral death to a mother with untreated or inadequately treated syphilis at delivery of a fetus weighing >500 g or >20 weeks" gestation ‘Modified and veprinted with permision:*” pharmacokinetics leading to lower serum con- centrations of penicillin in both the mother and the fetus." It is also possible that this time inter- val is insufficient for resolution of fetal infection, necessitating treatment for the newborn. Penicillin is the ONLY effective antimicrobial treatment for syphilis in the pregnant patient. In nonpregnant individuals, tetracycline, doxycy- cline, and erythromycin all have demonstrated efficacy. Tetracycline and doxycycline, however, are contraindicated in pregnancy because of staining of decidual tecth and impairment of ong-bone growth. Erythromycin should not be used because of the unpredictable. placental transfer of the drug: Infants have been born with the stigmata of congenital syphilis after ma- ternal treatment with erythromycin.°°*" Because no drug other than penicillin is ap- propriate for the pregnant patient with syphilis, ‘women with a penicillin allergy present a special problem. Nationwide, approximately 5% to 10% of individuals report sensitivity to penicillin. Tt is possible to safely identify those at risk for acute allergic reactions to penicillin with skin testing with the major and minor determinants. Women who have positive results should then undergo oral penicillin desensitization, which makes them temporarily tolerant to a course of paren- teral penicillin.” The desensitization protocol is ‘outlined in Table 5. None of the women who received recurrent therapy with long-acting pent «illin at intervals of I to 3 weeks had a detectable allergic reaction after the second or a subse- {quent injection." ‘The Jarisch-Herxheimer reaction commonly complicates therapy of early, acquired syphilis. Itis characterized by fever, chills, myalgia, head- ache, hypotension, tachycardia, and transient ac- centuation of any cutaneous lesions." It typically begins within several hours of treatment and re- solves after 24 t0 36 hours. In a study of 88 gravi- das with syphilis, 100% of women with primary syphilis, 60% with secondary syphilis, and none with latent syphilis had a Jarisch-Herxheimer re- action after administration of penicillin. The most common associated symptoms were fever (73%), uterine contractions (67%), and de- ‘ereased fetal movement (67%). Uterine contrac- tions and decreased fetal movement began con- ‘current with maternal fever in nearly all of the ‘women reporting contractions. Fetal tachycardia with decreased variability was common in associ- ation with maternal fever. Transient late deceler- ations were detected in 30% of the monitored. fetuses.” Although the mechanism of the reaction is not fully understood, elevated levels of prostaglan Fa and prostacyclin metabolites have been de- tected." Uterine contractions, pethaps mediated through prostaglandins, may progress to preterm labor and delivery in the case of the infected fe- tus. Stillbirth is another potential complication for the severely affected fetus.” Unforuinately, no prophylaxis against the adverse effects of treatment is available. For this reason, we recommend sono- graphic evaluation of the fetus if early syphilis is diagnosed in the third trimester. If the sono- ‘graphic evaluation is normal, hen the appropriate penicillin therapy can be administered on an out patient basis. Ifthe sonographic evaluation is ab- normal with evidence of fetal infection, hospitaliza- tion for therapy with fetal monitoring may be of benefit. Additionally, if severe fetal compromise is evident before initiation of therapy in a viable gestation, delivery with subsequent treatment of the mother and infant may result in an improved. ‘outcome.”*Gestational and Congenital Syphilis 329 Table 4. Recommended Treatment Regimens for Syphilis in Pregnancy Doseage Stage ‘Modieation| Primary Secondary Benzathine penicillin G Early latent Late latent Benzathine penicillin G 24 million units intramusculaely in single dose 7.2 million units total, administered as 3 doses of 24 million units intramusculaely weekly Some experts recommend a second dose I week later fora oul of 48 million units. Followup of titers is necessary to determine the adequacy of treatment.” After appropriate therapy, the titer of nontreponemal tests in pri- mary and secondary syphilis should decline four- fold after 3 to 6 months and eightfold by 6 to 12 months, and approach nonreactivty after about 12 months. Only about 72% of individu als with primary and 56% of those with secondary syphilis will have a nonreactive RPR by 36 months posttreatment. With early latent infec- tion, the fourfold fall in titer takes even longer— often about 1 year. Patients treated with late la tent syphilis may have even more prolonged in- tervals of declining titers. The effect of preg- nancy on the decline in titer is unknown, but titers in the gravida may fall more slowly than in nonpregnant adults” ‘Table 5. Oral Desensitization Protocol ‘Amount Dosages SMUT _ Cumulative Dose (a u w 1000 100 100 1000 03 300 300 1000 od 400 ‘700 300008 800 1,500 100016 1,600 3,100 100032 3.200, 6,300 1000 64 5,400 12,700 10000 «12 12,000 24,700 10000 24 = 24,000 45,700 10,000 48—48,000 96,700 80,000 «080,000 176.700 80,000 «20 160,000 386,700 30000 40 320,000 656,700 30,000 80 __640,000 1,296,700 Toteral between doses, 15 minutes: clapsed time, 8 hows and 4 minutes; cumulative dose, 1.3 milion units {The specific amount of pencil V suxpension was diluted tn approximately 90 mal of water and then given orally Modified and reprinted with permission.” Neonatal Therapy The decision to treat an infant for congenital syphilis is based on the elinieal presentation, pre- Vious maternal serology results and treatment, and results of the serologic testing of the mother and infant at delivery. Treatment is required in the following situations: a confirmed or pre- sumptive diagnosis of congenital syphilis, undoe- umented or unknown maternal therapy, mater- nal treatment within 4 weeks of delivery, insufficient fall in maternal titer in response to therapy or delivery before a fourfold fallin titer, ‘maternal treatment with drugs other than pe Gillin, or in situations in which infant follow-up ‘may be inadequate.” For asymptomatic infants the recommended dose of benzathine penicillin is 50,000 U/kg intramuscularly, up to the adult dose of 2.4 million units in a single dose.” Quantitative serologic testing should be per- formed at the 1, 2, 4, 6 and 12-month visi until the results revert to negative. Infants whose mothers were adequately treated in pregnancy may take up to 6 months to acquire negative serologic test results. Those who were treated in the neonatal period may take even longer to re- vert to negative but should have a nonreactive DRL in peripheral blood by 9 months and CSF by 6 months. A lumbar puncture should be re- peated at 6 months of age and the results com- pared with the neonatal CSF examination; if the VDRL js reactive, the child needs to be re- reated "7 References 1, Nakashima AK, Rolf RT, Flock ML, ea Epidemiology of syphilis in dhe United States, 1941-1001. Sex Transia Dis 2516-23, 1996 2 Gates W Je, Rothenberg RB, Blount JH: Syphilis control: ‘The historic context and epidemiologic basis for interaE OOOO een eee ee ee ee 330 18. 2. rupsing sexual transmission of Treponema politi, Sex “Transm Dis 286875, 1006 Evans HE, Frenkel LD Congenital syphilis, Clin Pevina- tol 21494162, 1994 Wendel GD: Gestational and congenital phils, Clin Perinatal 15287908, 1988, Harter C, Benischke K: Fetal syphilis the fist timer ter. Am J Obstet Gynecol 124:705-711, 1976 Nathan 1, Bohman VR, Sanchez J, eta Tn wero inf tian with Treponema pallidum in early peegnancy. Prenat Diag I7A1M4125, 1997 Webber MP, Lambert G, Bateman DA, et al: Materual Fisk factors for congenital phils case-control sud ‘Am J Epidemiol 137515422, 1903 Mefarlin BL, Bottom SF, Dock BS, etal: Epidemic syphi- lie Maternal factors sociated with congenital infection. Am J Ohstet Gynecot 1703535540, 1994 ‘Wendel GD Je Early al congenial aypili. Obstet Gye col Clin North Am 16:479-404, 1989 lack EG, Danbolt N: The Oslo study of dhe natueal couse of untreated phils: An epidemiologic ivestgn- tion base on the restdy ofthe Boeck Brousgaard ma terial. Med Clin North Amn 48:6134625, 1964 Kampmeier RH: Late benign sphilis, in Holmes KK, Mardh PA, Sparing FP, etal (ede) Sexually Transmitted Diseases. New York, NY, McGrail, 1984, p 338 Musher DM Editorial How much penicillin cues early syphili? 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