Performance of serologic tests for syphilis in special populations

Key Question

Do laboratory tests perform differently when applied to special populations such as HIV positive individuals or pregnant women? What tests should be used in cases of suspected congenital syphilis?

Literature Search Terms

((Treponema pallidum OR neurosyphilis OR syphilis) AND (sero-diagnos* OR serodiagnos* OR (serolog* AND (test* OR exam* OR assay* OR screen* OR lab* OR diagnos* OR nontreponemal OR treponemal OR algorithm* OR antibody titer)) OR serofast OR trimester OR rapid test*) NOT exp animals/ not exp humans/. Solely-based international studies were excluded from the literature search.

Grading

Four reviewers the evidence as high, medium, and low based on each study’s strengths and weaknesses. Case reports or small case studies were reviewed.

High quality publications: Studies using clinically characterized specimens, stratified by stage, larger sample size, prospective or a well-done cross sectional or retrospective study. Studies with large sample sizes, clinically characterized but not stratified by stage, or characterized but unclear exactly how it was done.

Medium quality publications: Studies with small sample sizes, moderate methodological issues, single lab test as gold standard, or descriptive.

Low quality publications: Studies with major methodological issues or small sample sizes.

I: Case reports or small case studies.

NR: Studies that were not relevant to the key question were assigned and not further rated.

Pregnancy
Citation Description of study type, design, population, and setting Reported findings, quantitative results related to key question Overall quality; strengths/weaknesses or limitations Relevance to the key question and/or overall importance Rank
Campos-Outcalt and Ryan

Prevalence of Sexually Transmitted Diseases in Mexican-American Pregnant Women by Country of Birth and Length of Time in the United States.

Journal of STDs Volume 22. Issue 2. Page 78-82. 1994

Prospective whole blood collection from one prenatal care clinic.

 

+MHA-TP with no treatment hx = case

 

VDRL followed by MHA-TP confirmation

Only one of 402 tested positive for syphilis All women were pregnant – no comparison to non-pregnant or comparison between tests

 

Only one positive syphilis

 

 

Not relevant to the key question NR
 Edwards et al.

Assessment of the Value of Recreening for Syphilis in the Third Trimester of Pregnancy.

Infect Dis in Obstet Gynec Volume 2006, Article ID 56504, Pages 1-3

Historic cohort analysis single hospital 7/1/03-6/30/04

 

Pregnant women only

 

“ Non-treponemal” confirmed using “treponemal”

 

Needed to start PNC <27 wks and deliver after 32 wks

 

Rate of screening calculated

No cases of syphilis were identified All women were pregnant – no comparison to non-pregnant or comparison between tests

 

Not relevant – no cases of syphilis identified and no comparison was done either between tests or between pregnant and non-pregnant population NR
Casal et al.

Risk factors and pregnancy outcomes in women with syphilis diagnosed using a molecular approach

Sex Transm Infect 2013 89: 257-261

Case-control study 1/06-12/08

Pregnant women single system Brazil

 

Case: Clinical and/or diagnosis syphilis

Control: Negative serology

Objective: Risk factor and preg outcomes

 

VDRL and FTA-ABS IgG, ELISA IgG, FTA-Abs IgM, nested PCR

 

Did define Early and Late stage categories using labs and clinical findings

 

Case: 169 Live births and 68 lethal

Contol: 219 live and 83 lethal

 

Outcome total

EMS – 17% clinical and 80% PCR+

LMS- 0% clinical and 42% PCR+

 

Outcome Liveborn:

EMS – 16% maternal clinical and 80% PCR+ mom

LLMS- 0% clinical and 40% PCR+ mom

 

Outcome Lethal: PCR+ mom in  81% miscarriage, 72.5% stillbirth and  83.3% neonatal demise with CS

 

Entire control population had a negative PCR

No clear comparison – no gold standard per se.

 

Conflicting results with

nPCR- limited sensitivity esp with latent disease

Nested PCR has limited sensitivity, esp with latent disease.

 

May help to predict which infants at highest risk for CS but not a good diagnostic tool alone

Medium
Galan et al

Retrospective Analysis of the Serologic Response to the Treatment of Syphilis During Pregnancy

Infectious Diseases in Obstetrics and Gynecology; 5:23-28 (1997)

Retrospective study 5 years UT Houston and Hermann

 

Inclusion- Maternal serology + RPR confirmed with MHA-TP

 

49 patients met inclusion of adequate treatment and follow-up. Excluded HIV

24 early latent and 20 unknown duration Inclusion into study required a positive RPR and MHA-TP

 

No comparison to a non-pregnant cohort and no comparison among tests

Looked at serologic response in pregnancy, not diagnostic tests specifically NR
Glover et al.

Diagnostic Considerations in Intra-amniotic Syphilis

Sex Transm Dis. 1985 Jul-Sep;12(3):145-9

Serology – VDRL and FTA-ABS

 

Amniotic fluid – Darkfield and immunofluorescent staining, VDRL, IgG IgA and IgM Technicon preciptin Rxn

 

Sample taken from one pt secondary syphilis

+ Darkfield amniotic fluid, + staining in the first sample (20 hours after RX), not in follow-up samples after treatment

 

VDRL in AF much lower than serum

 

IgM in AF may be associated with fetal infection

Samples obtained from only one patient so not able to make recommendations

 

Old techniques including IgM (? Antibody specificity)

VDRL poor measure  in amniotic fluid

 

AF IgM increased significantly in fetal infection (for this one case)

 

Spriochetes can be found in AF in secondary syphilis though in low concentrations

 

Overall importance low as only one case

I
Gomez et al.

Evaluation of the Bio-Rad BioPlex 2200 Syphilis Multiplex Flow Immunoassay for the Detection of IgM- and IgG-Class Antireponemal Antibodies

Clin Vaccine Immunol. 2010 Jun;17(6):966-8.

Gold standard: routine EIA screening (Trep-chek)

Bioplex 2200 Syphilis multiplex IgM and IgG

 

1008 prospective serum samples: 100% EIA and IgG and 67% IgM

 

Discrepant result repeat assay and TP-PA

Bioplex IgG 98.5% agreement with EIA

Bioplex IgG sensitivity 100% and spec 99.3%

 

Bioplex IgM 97.8% agreement with EIA

Sensitiv 100% and spec 98.5%

 

 

No clinical information While good comparison study, no pregnant patients were specifically identified NR
Harter and Benirschke

Fetal Syphilis in the first trimester.

Am J Obstet Gynecol. 1976 Apr 1;124(7):705-11

Syphilitic abortion material < 12 wks

 

Silver and IF staining

8 samples, no clinical findings in the mother

 

5 thought to be actually infected

 

40% (2/5) had spirochetes

Only pathology staining – no molecular or serologic No benefit – pathology confirmation, not screening or diagnostic testing for pregnant women Medium
Henrich and Yawetz

Impact of Age, Gender, and Pregnancy on Syphilis Screening Using the Captia Syphilis-G Assay

Sex Transm Dis. 2011 Dec;38 (12):1126-30.

Retrospective 52,238 samples

 

Captia IgG EIA with RPR and TP-PA testing (gold standard TP-PA confirm test)

 

46 pregnant women

Pregnant women with a +EIA, 53.5 % positive TP-PA concordance compared to 75.4% non-preg females (p=0.003) though not signif in a regression model (aOR 1.89, 0.84-4.26)

 

+EIA Preg 32.6% had +RPR versus 47.3% non-preg (p=0.065), aOR 1.48, 0.64-3.41)

 

If positive EIA and – RPR, TPPA + 28.6% preg vs. 56.5% non-preg (p=0.008) aOR 1.3, 0.45-3.8

 

Strong correlation between  IgG EIA and TP-PA is RPR positive with no change in pregnancy

 

 

 

 

Lower syphilis rates in women in this timeframe and population, leading potentially to higher false positive rates

 

Did not address disease stage

Pregnancy was associated with higher false positive rates of the Captia IgG EIA screening assay. High
Jonckheere et al.

Evaluation of different confirmatory algorithms using seven treponemal tests on Architect Syphilis TP-positive/RPR-negative sera

Eur J Clin Microbiol Infect Dis. 2015 Oct;34(10):2041

Architect Syphilis TP (CLIA with TpN15, TpN17 and TpN47) for IgM and /or IgG – high sensitivity, lower spec. (0.4-1.2% false positive rate)

 

Compared TP-PA confirmation to 3 immunoblots and 3 random access analyzers for women with Architect + (low S/CO between 1 and 15/RPR – samples

-recomLine Trep IgM and IgG

– Anti-Trep EUROLINE-WB IgM and IgG

-INNO-LIA IgG

-Chorus Syphilis screen

-Bioplex 2200 IgM and IgG

-Vitros Syphilis TPA

178 Architect +sera from 3 sites in Belgium

– 104 were TPPA positive 58%

Though stated that some of the patients came from “maternity”, no information was reported on type of patient, pregnancy status, clinical stage of disease, etc. TP-PA was the best confirmatory test (sens 89.5%, spec 92.2%)

 

Not pertinent to the key question

NR
Koskela et al.

Significance of False Positive Syphilis Reactions and Anticardiolipin Antibodies in a Nationwide Series of Pregnant Women

J Rheumatol. 1988 Jan;15(1):70-3.

Finland 20mos 1983-84. All tests performed at one center.

 

RPR card test with TPHA confirmation

 

aCL and ANA run on same samples

164 RPR positive samples with 13 positive for TPHA.

– half sera were negative in aCL assay

 

The false positive frequency 14/10,000

 

This was a study of False positive RPR and aCL and ANA correlation.

 

No information on the patients with syphilis

Not pertinent to the key question NR
Lefevre et al.

Evaluation of the Captia Enzyme Immunoassays for Detection of Immunoglobulins G and M to Treponema pallidum in Syphilis. J Clin Microbiol. 1990 Aug;28(8):1704-7.

VDRL, TPHA, FTA-ABS and 19S(IgM) FTA-Abs on all samples

 

Captia IgG and IgM

 

 

178 serum samples from clinically characterized pts

-96 untreated all TPHA/FTA-ABS +. Of these Captia IgG good except for primary

-82 treated pts

 

 

No information regarding pregnancy Captia IgG excellent sensitivity (98% overall) except primary (82%) so not as good as VDRL/TPHA as a screening tool

 

Not pertinent to the key question

NR
Manikowska-Lesinska et al.

Specificity of the FTA-ABS and TPHA tests during pregnancy

British Journal of Venereal Diseases, 1978, 54, 295-298

2000 pregnant women screened for syphilis

 

VDRL, TPHA, FTA-ABS and quant FTA – TPI if one was +

VDRL + 10 women

TPHA + 21 women

FTA-ABS + 13 women and 11 borderline

Older tests used

 

Small number of positive results limit conclusions

Neither the FTA-ABS nor TPHA test had a lower specificity in women during pregnancy.

 

Borderline FTA-ABS should be repeated and have TPHA or TPI performed

Medium
Marangoni et al.

Evaluation of the BioPlex 2200 Syphilis System as a First-Line Method of Reverse-Sequence Screening for Syphilis Diagnosis

Clin Vaccine Immunol. 2013 Jul; 20 (7):1084-8.

Bioplex 2200 Syphilis IgG and IgM compared to Architect Syphilis TP

 

RPR , WB and TPHA confirmatory tests

 

IgG and IgM WB Gold standard

 

Retrospective study from stored sera from several groups: blood donors, STD clinics, Architect + but negative TPHA,WB and RPR, Lyme disease, lupus, healthy adults

 

12 healthy pregnant women

Bioplex IgG and Architect showed 100% agreement with WB and TPHA overall

 

Bioplex IgG 89.7% specif versus 78.4% Architect, sens 100% for both

 

Bioplex IgM spec 94.9% send 84%

 

IgM best as an addition, not a replacement for IgG

 

 

No comparison among pregnant versus non-pregnant individuals

 

CS should only be ruled out using WB IgM

Not pertinent to the key question NR
McFarlin and Bottoms

Maternal Syphilis:  The Next Pregnancy

Am J Perinatol. 1996 Nov;13(8):513-8

Retrospective chart review of women with syphilis and at least 2 consecutive preg

 

RPR and FTA-ABS positive women

 

No test comparisons

 

 

46 women identified: 85 live births, 7 stillbirths and 2 neonatal death. 40 infants with CS

 

RPR titers were not significantly associated with CS in subsequent preg

 

Slow seroreversal in pregnant women after treatment

Not a test comparison – this was descriptive study of women with syphilis and infant outcomes Not pertinent to the key question NR
Mmeje et al. Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and Implications for Clinical Management. Clin Infect Dis. 2015 Oct 1;61(7):1049-53 Retrospective analysis

 

194 Pregnant patients aged ≥ 18 years

 

Kaiser Permanente Northern California (KPNC)

 

156 (80%) were CIA +/RPR−/TP PA− and 38 (20%) were CIA+/RPR−/TP-PA+.

 

Among the 77 (49%) CIA+/RPR−/TP-PA−, women who were retested, 53% became CIA−

 

 

The analysis was based on observational data and therefore systematic retesting of all pregnant patients was not performed

Exact number of pregnant women who were screened was not recorded

Findings not generalizable – prevalence of syphilis in KPNC is low (2%)

 

CIA+/RPR−/TP-PA− serology in pregnancy is likely to be falsely positive.

Most pregnant women with discordant serology were CIA+/RPR−/TP-PA−

 

Reflexive testing of discordant specimens with TP-PA is important to stratify risk given the likelihood of false-positive results

High
Peterman et al. Do women with persistently negative nontreponemal test results transmit syphilis during pregnancy? Sex Trans Dis 2013, 40 (4); 311-5 Ecological study

23,863 patients with congenital syphilis with birthdates between 1991 and 2009

Of 106 mothers initially classified as having only negative non-treponemal test results, 20 were misclassified

 

The remaining 86 mothers had no infants with confirmed syphilis and no syphilitic stillbirths

 

The 23,757 other mothers had 284 (1.2%) infants with confirmed syphilis and 1271 (5.4%) syphilitic stillbirths

There is no convincing evidence of syphilis transmission from mothers with persistently negative non-treponemal test results in pregnancy.

Only 1 case suggested that transmission may have occurred, and records were incomplete.

Weaknesses of an ecological study.

Persistently negative syphilis testing in pregnancy has a high negative predictive value. Medium
Rac MW et al. Maternal titers after adequate syphilotherapy during pregnancy. Clin Infect Dis. 2015 Mar 1; 60(5):686-90.

 

Retrospective cohort study

166 patients who had prenatal care at University of Texas Southwestern Medical Center, Dallas from September 1984 to June 2011 diagnosed with syphilis after 18 weeks of gestation.

 

Mean gestational age at treatment was 29.1 ± 5 weeks

93 (56%) women were diagnosed with early-stage syphilis

For all stages of syphilis, maternal titers declined after syphilotherapy.

Pretreatment titers were higher and declined more rapidly in primary and secondary disease than in latent-stage disease and syphilis of unknown duration.

38% of patients achieved a 4-fold decline by delivery.

Patients without a 4-fold decline by delivery were older, diagnosed with latent syphilis or syphilis of unknown duration.

One of the largest cohort describing the serologic response to syphilotherapy

The drawbacks of retrospective cohort study

Research in a single institution (limited external validity)

Incomplete infant outcomes.

 

Serologic response is similar in the pregnant and non-pregnant populations

Slower serologic response to syphilotherapy also seen in older age

9 months of gestation is insufficient to achieve an “adequate serologic response per CDC definition.

High
Rawstron SA et al. Comparison of maternal and newborn serologic tests for syphilis. Am J Dis Child, 1991; 145(12):1383-8. Retrospective cohort study

Compared maternal and fetal cord blood samples in babies diagnosed with congenital syphilis

115 newborns (33%) had negative RPR testing in the setting of a positive maternal syphilis test

10% false positive and 5% false negative testing

Maternal serology is superior to cord blood analysis for identifying newborns at risk of congenital syphilis. Consistent with practice in non-pregnant populations. High
Thornton JG et al. False positive results of tests for syphilis and outcome of pregnancy: retrospective case-controlled study. B Med J, 1987; 295 (6594): 355-6 Retrospective case controlled study

64 women with false positive syphilis test, and 128 controls matched for age, parity, hospital of delivery and year of delivery.

Study showed that women with false positive syphilis result in pregnancy had increased rate of pregnancy loss. Non nested case controlled study

Inherent problem with this study design is that since the disease occurred before the outcome, there is possibility of recall bias and misclassification.

Frequency of false positive syphilis testing lower in pregnancy compared to the general population. Medium
Yeganeh N. Syphilis in HIV-infected Mothers and Infants, Results from the NICHD/HPTN 040 Study. J Pediatr Infect Dis J. 2015; 34 (3): E52-7. 10% of women (n =171) enrolled had serological evidence of syphilis without adequate treatment documented and 1.4% infants (n = 24) were dually HIV and syphilis infected. Compared with HIV-infected or HIV-exposed infants, co-infected infants were significantly more likely to be born to mothers with venereal disease research laboratory titers ≥1:16 Retrospective cohort study. Syphilis continues to be a common co-infection in HIV- infected women and can facilitate in utero transmission of HIV to infants. NR
Sperling RS et al. HIV Sero-prevalence in pregnant women testing positive for syphilis. The Mount Sinai Journal of Medicine, 1992, 59(1); 67-8 Paper describing frequency of HIV/Syphilis co-infection in pregnancy. No specific description of syphilis testing in pregnant women. NR
Thomas PA et al. Maternal predictors of perinatal human immunodeficiency virus transmission. Pediatr Infect Dis J, 1994; 13:489-95 Paper that identified characteristics of pregnant HIV-1 infected women that predicted HIV transmission from mother to child. No specific mention of syphilis in this paper. NR
Yang et al. Comparison of serological responses to single dose azithromycin (2g) versus benzathine penicillin G in the treatment of early syphilis in HIV-infected patients in an area of low prevalence of macrolide-resistant Treponema pallidum infection. J Antimicrob Chemother. 2016, 71; 755-82. Study describes the effectiveness of single-dose azithromycin (2 g) in the treatment of early syphilis among HIV-infected patients in the era of combination ART.

 

No description of syphilis testing in pregnancy in this paper. NR
O’Connor M et al. Syphilis in pregnancy. J Midwifery Women’s Health. 2008; 53 (3): e17-21. Review article of congenital syphilis Not a laboratory study, but a review article on congenital syphilis NR
Parker AL et al.  The prevalence of antiphospholipid antibodies in women with recurrent spontaneous abortion, women with successful pregnancies, and women who have never been pregnant. Arthritis Rheum. 1991; 34 (10): 1231-5. The paper describes the relationship between antiphospholipid antibodies and connective tissue diseases. No description of syphilis in this paper. NR
Congenital Syphilis
Citation Description of study type, design, population, and setting Reported findings, quantitative results related to key question Overall quality; strengths/weaknesses or limitations Relevance to the key question and/or overall importance Rank
Bennett et al.

Congenital syphilis:  Subtle presentation of fulminant disease

J Am Acad Dermatol 1997;36:351-4

Case report CS diagnosed after delivery

 

No gold standard discussion

 

Maternal RPR NR in pregnancy

Histology placenta acute chorioamnionitis

 

Infant developed papulosquamous eruptions 3 weeks after birth

 

RPR 1:512 with +FTA-ABS, leukocytosis, TCP, anemia, LFT abnormality. CSF RPR negative

 

Skin biopsy Steiner stain positive for spirochetes in epidermis

 

X-Ray abnormalities

Case report

 

No discussion lab test other than recommending more frequent testing during pregnancy

Does not answer the question regarding laboratory test performance NR
Chhabra et al

Comparison of Maternal Sera, Cord Blood, and Neonatal Sera for Detecting Presumptive Congenital Syphilis:  Relationship with Maternal Treatment

Pediatrics Vol. 91 No. 1 January 1993;91;88

Bronx Municipal Hospital Center

 

No gold standard discussion

 

Infants born to a mother with +RPR have cord blood and sera RPR performed 2-3 days of age. FTA-ABS confirmation

 

Retrospective review of all +RPR mother/infant pairs

73 newborns (72 mothers) – 4 moms seronegative at delivery

–         7/73 had clinical and/or laboratory CS

-1 newborn died of CS

 

If mother not treated, 66% cord blood and 86% neonatal sera positive (not signif)

 

If mother treated, 36% cord and 39% neonatal sera +

 

6 mothers + only at delivery – all neonatal sera +, 50% cord blood +

Retrospective but addresses the question. Uses standard lab techniques and discusses limitations of the current testing e.g. prozone reaction, treatment timing Maternal sera more likely to be positive than cord or neonatal serum in infant at risk for CS – need maternal and neonatal sera tested

 

Cord blood alone may miss 50% CS infants

High
Dorfman and Glaser

Congenital Syphilis Presenting in Infants After the Newborn Period

N Engl J Med. 1990 Nov 8;323(19):1299-302

Retrospective chart review – infants admitted to Albert Einstein 12/88-11/89 with CS – no maternal h/o syphilis RX, both mother and infant (cord blood)serology negative at birth

 

Infants admitted had RPR and FTA-ABS

 

Not all mothers had testing at delivery (4/7 tested) and 6/7 infants tested at delivery (cord)

7 infants met criteria, becoming symptomatic at 3-14 weeks of age. All had evidence multi-organ disease. 4/7 abnl LPs with 2/7 abnl VDRL

7/7HSM

4/7 rash

3/6 abnl long bones

7/7 RPR 1:16-1:512

5/5 moms tested when child admitted had a positive RPR 1:8-1:256

Good review of problems with lab testing in mother/infant pairs with probable infection near delivery – timing +/- prozone Rx Mothers should be tested at least at first PNC visit and again at delivery

 

All infants should be tested at delivery

I
Frecentese and Schreiman

Congenital Syphilis in Nebraska:  A Case Report

Nebr Med J. 1991 Oct;76(10):330-4.

Case Report infant delivering at 36 weeks gestation. Maternal VDRL 7 months earlier NR, no delivery testing Infant VDRL 1:64, +FTA-ABS

CSF VDRL NR

Long bone bone scan abnormal

No retesting performed at delivery for mother and no neonatal testing

 

No lab comparison or discussion

 

 

Long bone survey important in evaluation

 

Testing at delivery mother and infant important

 

Does not answer the question regarding lab test performance

NR
Greenberg and Bernal

Are Long Bones Radiographs Necessary in Neonates Suspected of Having Congenital Syphilis?

Radiology. 1992 Mar;182(3):637-9.

93/104 infants with suspected CS had long bone radiography

 

All had +RPR,  MHATP and/or autopsy finding

 

No gold standard

Long bones abnl in 19%

 

10/93 had negative RPR but +MHATP

 

No false negative MHATP

State MHATP better diagnostic test than RPR for CS but do not address passive vertical antibody transfer Serologic testing better than long bone analysis for diagnosis

 

Long bone conclusion not justified

 

 

Medium
Hallock and Tunnessen

Congenital Syphilis in an Infant of a Seronegative Mother

Obstet Gynecol. 1968 Sep;32(3):336-8

Case report 2 month old infant diagnosed with CD Mom had Kolmer and Kline testing which was negative first trimester. Clinical findings c/w secondary 6 months but not seen

Infant and mother not tested at birth

 

VDRL +, +long bones and CSF

Case report – no lab discussion Does not answer the question regarding lab test performance NR
Jonna et al.

Postneonatal Screening for Congenital Syphilis

J Fam Pract. 1995 Sep;41(3):286-8.

District of Columbia

Case series of 3 infants who were seronegative at birth

 

7-8 weeks seropositive

2 developed a rash and one asymptomatic but mother diagnosed on PP visit

Discussion of why neonatal serology may be negative at delivery Does not answer the question regarding lab test performance NR
Levine et al.

Nonimmune Hyrdrops Fetalis Due to Congenital Syphilis Associated with Negative Intrapartum Maternal Serology Screening

Am J Perinatol. 1998 Apr;15(4):233-6

Case report 29 week gestation non-immune hydrops. Maternal RPR negative at delivery – after neonatal death, record review RPR early in pregnancy positive Neonatal evaluation – abnl long bones, RPR 1:16, MHATP positive. Autopsy

 

Maternal serum diluted and prozone phenomenon 1:1024 RPR

No mention if prozone phenomenon more common in pregnant vs non-pregnant individuals Serum dilution important if clinical evidence of maternal or CS infection I
Lewis.

Congenital Syphilis

Serologic Diagnosis in the Young Infant

Infect Dis Clin North Am. 1992 Mar;6(1):31-9

Review article of tests used to diagnose CS No data – review only Does not answer the question regarding lab test performance NR
Marangoni et al.

Evaluation of the BioPlex 2200 Syphilis System as a First-Line Method of Reverse-Sequence Screening for Syphilis Diagnosis

Clin Vaccine Immunol. 2013 Jul; 20 (7):1084-8.

Bioplex 2200 Syphilis IgG and IgM compared to Architect Syphilis TP

 

RPR , WB and TPHA confirmatory tests

 

IgG and IgM WB Gold standard

 

Retrospective study from stored sera from several groups: blood donors, STD clinics, Architect + but negative TPHA,WB and RPR, Lyme disease, lupus, healthy adults

 

12 healthy pregnant women and 10 sera from babies born to infected mothers

Bioplex IgG and Architect showed 100% agreement with WB and TPHA overall

 

Bioplex IgG 89.7% specif versus 78.4% Architect, sens 100% for both

 

Bioplex IgM spec 94.9% send 84%

 

IgM best as an addition, not a replacement for IgG

 

Bioplex syphilis 2200 IgM + for the one CS case in the cohort

 

 

CS should only be ruled out using WB IgM If using IgM, IGM WB better than MFI method Medium
Meyer and Malan

Rheumatoid factor in congenital syphilis

Genitourin Med 1989;65:304-307

Peninsula Maternity and Neonatal Service

 

Group 1: Neonates whose mothers were VDRL+/ TPHA+ with untreated, inadequately treated or within 1 month

Group 2: Controls negative testing mother and neonate

 

Neonatal sera – RF latex agglutination, Total IgM radial immunodiffusion plate, VDRL and TPHA, FTA-Abs IgM

 

Group 1: 69 infants (14 moms treated within 1 month, 5 with erythro, rest untreated.

– 15 infants with CS

–  only 1 had VDRL > maternal titer

– 4 symptoms

– 8 had negative RF

– 7 had total IgM increased

– 12 +VDRL

– 4 + FTA-Abs IgM

Overall RF sensitivity 46.7%

Specificity 100%, Pos pred value 100%, Neg predictive value 86.4%

 

FTA-Abs IgM sens 26.6%

Total IgM 46.7%

 

Of 84 controls Total IgM increased in 4

 

Does not incorporate any of the newer tests but solid study design for the older test comparison While sensitivity of RF in symptomatic pts higher (75%) (no symptoms only 36.4%), not a good screening or diagnostic test

 

VDRL titer higher than maternal titer not useful

 

No test studied was sensitive enough to rule out CS in asymptomatic infants

 

High
Page et al.

Diagnostic Tests for Evaluation of Stillbirth. Results From the Stillbirth Collaborative Research Network

Obstet Gynecol. 2017 Apr;129(4):699-706

Secondary analysis NICHD stillbirth network 512 stillbirth cohort

512 had placenta pathlogy

507 RPR and FTA-ABS

No syphilis testing results were reported not were any cases of CD reported in the cohort Does not answer the question regarding lab test performance NR
Pedersen et al.

Enzyme-Linked Immunosorbent Assays for Detection of Immunoglobulin M to Nontreponemal and Treponemal Antigens for the Diagnosis of Congenital Syphilis. J Clin Microb. 1989. Vol 27. P1835-40

Group 1: 84 pregnant women in Botswana 1986. Maternal and cord blood

 

Group 2: Zambia 10 mothers with RPR+ and no treatment  Maternal and cord blood

 

Group 3: Zambia 15 mothers RPR+ with treatment  Maternal and cord blood

 

RPR, FTA-ABS, flagellum ELISA, VDRL ELISA IgM and IgG, neonate blood also RF by ELISA

 

Group 1 Neonate sample 1 with CS

VDRL IgG (16.7%), IgA (1.2%),   IgM (1.2%)

Flagellum ELISA IgG (33.3%), IgM (1.2%)

FTA-ABS IgG/IgA/IgM (34.5%), IgM (1.2%)

 

Group 2 Neonatal sample – all had evidence CS clinically

VDRL IgG (100%), IgA (70%),   IgM (90%)

Flagellum ELISA IgG (100%), IgM (90%)

FTA-ABS IgG/IgA/IgM (100%), IgM (90%)

6/8 had a positive RF IgM

5/10 had higher VDRL than the maternal titier

 

Group 3: Neonatal Sample 4 clinical HSM

VDRL IgG (80%), IgA (13.3%),   IgM (13.3%)

Flagellum ELISA IgG (100%), IgM (13.3%)

FTA-ABS IgG/IgA/IgM (100%), IgM (6.7%)

0/15 RF IgM

 

 

Some infants with CS had non-reactive tests  – late pregnancy infection may be negative at birth VDRL ELISA and the flagellum ELISA for IgM useful, (VDRL ELISA inexpensive and not labor intensive). False positive rare. Not significantly affected by RF IgM

 

FTA-ABS IgM reactivities weaker ? IgM/IgG competition

 

Fetus/neonate may not respond as well to flagellum ELISA IgG as none had a higher titer than the mother –

 

IgA does not cross placenta –may be a useful supplement

High
Rawston SA et al. Congenital syphilis – detection of treponema pallidum in Stillborns. Clin Inf Dis 1997; 24: 24-7. 1/1987-12/1989, 392 stillbirths at Kings County NY

17 (30%) of 56 cases of stillbirth associated with a positive RPR, confirmed by a reactive FTA-ABS

29.8 weeks median, 30 weeks; mode, 38 weeks; and range, 20-38 weeks.

Congenital syphilis was diagnosed in 9/17 cases on the basis of silver stain or morphology alone.

IFA testing diagnosed 15/17 cases of stillbirth.

Only a minority of these stillborn babies whose mothers were RPR positive were available for evaluation.

Majority of the mothers refused autopsy.

 

 

Most stillbirths associated with a reactive maternal RPR test during pregnancy involved congenital syphilis

Immunofluorescent antibody testing (IFA) testing for T. pallidum is superior to silver staining for the identification of treponemes.

Medium
Rawston SA et al. Evaluation of a treponema pallidum-specific IgM enzyme immunoassay and treponema pallidum western blot antibody detection in the diagnosis of maternal and congenital syphilis. Sex Trans Dis 2004; 31 (2): 123-26

 

Ninety-seven mother–baby pairs with reactive syphilis serology at Kings County NY

 

Treponemal pallidum (TP) IgM Western blot tests were positive in 18 pregnancies (7 of 18 babies had congenital syphilis(CS) & negative in 79 pregnancies (7 of 82 babies had CS). 32 mothers had titers >1:16 (6 babies with CS) and 65 moth- ers had titers <1:8 (8 babies with CS).

 

Retrospective cohort study, hence causality cannot be established. TP IgM tests better identify mothers at risk of delivering babies with CS than maternal titer >1:16.

 

Medium
Reyes, PM et al. Maternal/congenital syphilis in a large tertiary hospital. Clin Inf Dis 1993;17:1041-46 9,591 infants in 1990 at Hutzel Hospital in Detroit, Michigan

Mothers are primarily young, black, multigravid women with a history of crack cocaine use

 

 

148 had positive results in the rapid plasma reagin (RPR) and fluorescent treponemal antibody– absorption tests for syphilis.

 

 

 Retrospective cohort study, inherent problems with missing data

Study did not identify mothers with a negative syphilis testing, with infants testing positive for congenital syphilis.

Study described maternal risk factors for acquisition of syphilis in pregnancy NR
Rawston SA et al.  Congenital syphilis and fluorescent treponemal antibody test

reactivity after the age of 1 year. Sex Transm Dis 2001; 28 (7):412-6

Prospective outpatient follow-up study.

Babies born at KCHC between 1/1/89-1/1/94 to mothers with reactive syphilis serologies

54 children had reactive FTA-ABS at >12 months, of which 17 (31%) were confirmed with syphilis at birth

142 children had nonreactive FTA-ABS (nonreactors) at >12 months. 14 of the 142 (10%) had confirmed syphilis at birth

 

Not all the children received either a full clinical or laboratory evaluation at birth

Not every test result for syphilis was positive in every infected baby.

A reactive FTA-ABS may be seen at 12 months in children with and without evidence of congenital syphilis at birth.

Not all children with congenital syphilis will manifest reactive FTA-ABS at 12 months

FTA-ABS reactivity wanes with time.

High
Reed D et al. Challenges in the diagnosis and treatment of congenital syphilis. Conn Med. 2012 ;76(7):397-400. Case report describing the consequences of untreated syphilis in pregnancy in the era of effective antibiotic therapy for Treponema pallidum. Case of congenital syphilis in a dichorionic-diamniotic twin pregnancy that resulted in a stillbirth of one twin and the characteristic findings of congenital syphilis in the surviving twin. Case report

 

Demonstrates a number of challenges to the clinician in the effective and timely diagnosis and treatment of syphilis in pregnancy. Not relevant to the clinical question. I
Rosen EU et al. A reappraisal of the value of the IgM fluorescent treponemal antibody absorption test in the diagnosis of congenital syphilis J Pediatr. 1975; 87(1):38-42 Three groups of infants were tested:

Group 1 – 20 uninfected infants whose mothers had negative serology for syphilis the FTA-ABS, IgG FTA, and IgM FTA tests were completely negative

Group 2 – 115 symptomatic infants who had positive FTA-ABS tests

Group 3 – From the results of the fluorescent absorption tests carried out during the first week of life, this group of asymptomatic infants with possible treponemal infection

 

Group 1 infants showed that the test was always negative in normal neonates born to seronegative mothers.

Group 2 infants allowed for standardization of the test using commercially prepared conjugate to allow the maximum exclusion of false positive and negative results

Group 3 neonates confirmed Treponema pallidum

Occasional false negative/positive results occurred with the IgM FTA test IgM FTA test, if suitably standardized, is a highly successful method for diagnosing congenital syphilis, especially in asymptomatic neonates. Medium
Sheffield JS et al. Placental histopathology of Congenital Syphilis. 2002. Obstet and Gynec. 100:126-133. Retrospective cohort 1/86-12/98

 

Included women with untreated syphilis who had placenta evaluated

 

VDRL or RPR with FTA-ABD or MHATP (change over time). Stage disease included

 

CS diagnosed by exam, anemia, TCP, or VDRL in CSF, abnl long bone, serum IgM immunoblot, serum, blood or CSF PCR, RIT or Darkfield +.

67 women included: 33 stillborn with CS, 18 liveborn CS, 15 uninfected infants and 1 stillborn without CS

 

PE, abnl long bone, CSF VDRL, Serum IgM immunoblot, PCR + and RIT + all predictive CS

 

Nec funisitis, villous enlargement, acute villitis, fetal vasculopathy and erythroblastosis all predictive of CS

Placental histology review

 

No absolute placental finding associated with CS

Placental histology useful additional test for CS diagnosis – picks up more cases of CS than PE and lab alone in asymptomatic infants and stillborn infants with CS Medium
Sheffield JS et al.  Congenital syphilis after maternal treatment for syphilis during pregnancy.  Am J Obstet Gynecol 2002;186:569-73 Retrospective cohort study from 1/1/82 – 12/31/98 involving women who received antenatal treatment for syphilis

Infants who were born with congenital syphilis were identified by clinical or laboratory criteria

43 women who received treatment antenatally for syphilis had babies with congenital syphilis

Mean gestational age at treatment was 30.3 weeks.

35% of women were treated for >30 days before delivery

Being retrospective in nature, comparability between infants exposed to syphilis and those not exposed is difficult to measure. High VDRL titers at delivery, earlier maternal stage of syphilis, the interval from treatment to delivery, and delivery before 36 weeks’ are associated with congenital syphilis even after adequate maternal treatment NR
Srinivasan G et al. Congenital syphilis: a diagnostic and theraupetic dilemma.  Pediatr Infect Dis. 1983; 2(6):436-41. Prospectively evaluation to derive diagnostic and therapeutic criteria for congenital syphilis 78 infants with serologic evidence of syphilis (+RPR, +FTA)

61 asymptomatic infants (-RPR, -FTA)

8 infants positive for congenital syphilis

9 infants with late onset infection

Elevated serum  IgM noted in infants with congenital syphilis

Information on some of the infants could not be obtained because they were lost to follow up. The incidence of CNS involvement in congenital syphilis appears to be extremely low.

The value of routine spinal fluid examination is low yield

Medium
Talati AJ et al.  Neonates at risk for congenital syphilis: radiographic and cerebrospinal fluid evaluations.  South Med J. 2011 Dec;104(12):827-30 Retrospective chart review of all of the infants at risk for congenital syphilis from 1/1/97 – 12/31/2002 at the Regional Medical Center at Memphis

Subjects were identified from a database of prenatal maternal records

From 24,245 deliveries, maternal serology (RPR & MHA-TP) was reactive in 250 women during pregnancy.

Of 92 infants with a presumptive diagnosis of syphilis, only 2 (2.1%) were symptomatic

Retrospective cohort study and its inherent problems

No follow-up beyond the newborn period

Routine use of radiography studies was not addressed.

The frequency of positive CSF and long bone radiography studies is extremely low Medium
Teberg A. Congenital syphilis in newborns. Calif Med. 1973; 118: 5-10. Case series involving 6 cases of congenital syphilis at Los Angeles County, USC, California over a 7 months  period No single clinical symptom was present in all case

Symptomatic infants had radiographic evidence of bone disease.

Case series – Problems with selection bias and small sample size Case series.  Did not address specific laboratory testing. NR
Wendel GD et al. Examination of amniotic fluid in diagnosing congenital syphilis with fetal death.  Obstet Gynecol. 1989; 74(6):967-70. 5 pregnant women with congenital and untreated syphilis and fetal deaths had sonographic examination and amniocentesis. Dark-field examination of the amniotic fluid showed spirochetes consistent with Treponema pallidum Limited sample size (5 patients). Dark-field microscopic exam of spirochetes is recommended for women with syphilis and a fetal death, especially if sonographic hydrops and/or edema is present I
Wendel GD et al.  Identification of treponema pallidum in amniotic fluid and fetal blood blood from pregnancies complicated by congenital syphilis. Obstet Gynecol 1991; 78 (5): 890-5. Case series (2 patients) with secondary syphilis s/p amniocentesis for congenital syphilis In both cases, motile spirochetes, typical of Treponema pallidum, were observed during dark-field microscopic examination of the amniotic fluid Small sample size (only 2 patients in the series). Presence of T pallidum in amniotic fluid or fetal blood indicates fetal-placental infection I
Wozniak PS et al. Congenital syphilis in neonates with nonreactive nontreponemal test results. 2017. J Perinatology 37:1112-1116

 

Retrospective 1984-2002

 

+ maternal RPR or VDRL confirmed with MHA-TP or TPPA

 

Neonates with norml PE and nonreactive RPR or VDRL

 

IgM immunoblot (Tp72,47,45,42,37,17,15kDa), PCR 47kDa serum, blood or CSF, RIT

794 women with + serology delivered 115 infants with NR VDRL/RPR. 87 born to mothers untreated, 14 treated <4 weeks before delivery

 

4/87 infants untreated mothers had a + molecular test

 

1/14 treated <4 weeks before delivery had a + molecular test

Limited follow-up and not all tests were performed on all subjects.

 

Retrospective over a long period – changing availability of testing

Contribution to the key question is limited – stresses that CS diagnosis remains difficult. Medium
Persons living with HIV
Citation Description of study type, design, population, and setting Reported findings, quantitative results related to key question Overall quality; strengths/ weaknesses or limitations Relevance to the key question and/or overall importance Rank
Andrade et al

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV:  A Randomized Clinical Trial

Clin Infect Dis. 2017 Mar 15;64(6):759-764.

Prospective randomized open label study

HIV infected with untreated early stage disease

RPR and TP-PA, clinical staging

BPG x 1 dose vs.3 doses over 3 weeks

Treatment success RPR decrease 2 dilutions or more in 12 months

64 total (35 and 29)

 

Success rates 80% vs 93% (P=0.17)

 

RPR titer at start not a factor

Solid RCT to answer a treatment question – not able to answer lab testing in HIV versus non-HIV population Not relevant to the key question NR
Andrade et al

Acute HIV infection presenting as fulminant meningoencephalitis with massive CSF viral replication

Neurol Clin Pract. 2014 Jun;4(3):256-259.

Case report

 

HIV positive

 

No syphilis

Not a syphilis patient

 

Not relevant to the key question NR
Appleman et al

Cerebrospinal Fluid Abnormalities in Patients Without AIDS Who are Seropositive for the Human Immunodeficiency Virus

J Infect Dis. 1988 Jul;158(1):193-9

9/86-12/86

 

HIV + WB

 

Extensive lab evaluation including RPR and FTA-ABS, CSF VDRL

117 confirmed WB+

 

27% +FTA-ABS

 

15 treated for active syphilis

 

Abnl CSF not associated with abnl syphilis testing

 

2 evidence neurosyphilis

Limited applicability as this is a look at CSF abnormalities in HIV, regardless of syphilis testing.

 

Negative CSF VDRL does not exclude neurosyphilis

 

No other conclusions with regards to syphilis testing and HIV

Medium
Augenbraun et al

Treponemal Specific Tests for the Serodiagnosis of Syphilis

Sexually Transmitted Diseases: November 1998 – Volume 25 – Issue 10 – p 549–552

Gold standard RPR with treponemal confirmatory

 

Multi-site eval of pts with early stage syphilis by serology or microbiology

RPR, MHATP and FTA-ABS

 

HIV testing performed

 

BPG +/- amox/probenecid

525 pts enrolled – 104 HIV+

 

128 primary, 243 secondary and 139 early latent

 

MHA-TP vs FTA-ABS discordance overall 4%, 11% primary, 10% HIV+

 

No signif difference in FTA-ABS or MHA-TP follow-up seroconversion

Solid study design with large numbers

 

Appropriate testing algorithms

 

Large number of lost to follow-up at 1 year

 

 

HIV serostatus not associated with a lack of TST reactivity in untreated early stage syphilis High
Augenbraun et al

Biological False-Positive Syphilis Test Results for Women Infected with Human Immunodeficiency Virus

Clin Infect Dis. 1994 Dec;19(6):1040-4

9/1991-5/1993 156 HIV infected women Brooklyn prospectively enrolled compared to 633 HIV non-infected women

 

RPR with MHA-TP confirmation. If discordant, FTA-ABS performed.

 

Biological false positive (BFP) = RPR+/MHA-TP-/FTA-ABS-

5.8% BFP HIV + vs 0.2% HIV non-infected (20-fold higher)

 

25% reactive RPRs in HIV infected cohort were BFP

 

Assoc with IVDU but not CD4 count, demographic or social factors

 

? loss TST response over time as 3 pts h/o syphilis

Comparison from women from 2 different studies. That being said, standard testing algorithms. Comparison appropriate. Emphasizes need for confirmatory testing, esp if h/o IVDU

 

No direct comparison with other tests

High
Becerra et al

Syphilitic Uveitis in Human Immunodeficiency Virus-infected and Noninfected Patients

Ophthalmology. 1989 Dec;96(12):1727-30

Case series of 25 pts with uveitis and + RPR/+MHA-TP 1986-1988

 

8 did not have HIV testing and excluded

 

 

12/17 were HIV positive, RPR titers 1:8-1:8192

 

All 12 had abnl LP 6/12 +VDRL

Case series

 

Limited testing data outside of RPR, MHA-TP and CSF

High CSF abnormalities in this cohort – may be secondary to syphilis versus HIV

 

Medium
Berger

Neurosyphilis in Human Immunodeficiency Virus Type 1 – Seropositive Individuals

Arch Neurol. 1991 Jul;48(7):700-2

Prospective study South Florida w 3 groups: HIV-1 -, neuro asympt HIV + and neuro symptomatic HIV+

 

RPR and FTA-ABS performed on all pts enrolled, LPs all HIV+ and some HIV-

338 subjects (72 HIV-, 187 asx HIV+ and 79 Sx HIV+)

 

FTA-ABS + 46% HIV+ vs 17% HIV- (high prevalence prior syphilis)

 

RPR 5.6% HIV- vs 9.6% HIV+

 

20 HIV+ RPR – 15% had a reactive CSF VDRL

Prospective trial

 

Objective not specifically the Key question

Rate of unsuspected neurosyphilis higher in HIV+

 

All neurosyphilis pts had reactive serum FTA-ABS and reactive RPR though non-reactive RPR cannot rule out neurosyphilis based on this data

 

NR CSF VDRL does not exclude neurosyphilis

NR
Berger

Spinal cord syphilis associated with human immunodeficiency virus infection: A treatable myelopathy. Am J Med. 1992; 92:101-103

Case report HIV +, RPR+ +FTA-Abs. CSF FTA-ABS+, VDRL-, pleocytosis Neurosyphilis but CSF VDRL- Case report with no lab discussion other than neurosyphilis may present with a neg CSF VDRL Not responsive to the key question NR
Bordon et al

Response to Standard Syphilis Treatment in Patients Infected with the Human Immunodeficiency Virus

Eur J Clin Microbiol Infect Dis (1999) 18: 729-732

HIV infected pts with confirmed syphilis (RPR and TPHA) – LP for VDRL, leuko cts (initial and last eval), RIT and PCR for TP DNA (47kDa) (last eval)

 

Purpose was to eval lab response after therapy

13 pts enrolled – 8 males and 5 females)

 

4pts primary, 5 latent and 4 neurosyphilis (VDRL +3/4)

 

RPR declined +/- went to NR in all 13

Unable to determine utility of PCR for diag and assessment of treatment response to neurosyphilis

 

Very small series

Suggested treatment appropriate for HIV infected persons with syphilis but did not address the key question NR
Bristow et al

Laboratory Evaluation of a Dual Rapid Immunodiagnostic Test for HIV and Syphilis Infection

J Clin Microbiol. 2015 Jan;53(1):311-3.

Stored serum specimens Peru STD clinic

 

Gold standard -4th generation Genscreen, WB confirmed and a Serodia-TPPA and RPR

 

Compared to Multiplo Rapid TP/HIV

200 serum samples  – 198 validated and used

 

HIV – 84+. Sens 100%, spec 91.9%

 

TP – 104+. Sens 94.5%, sens 92.8%

High risk, high prevalence population for HIV and syphilis

 

Stored samples and no clinical correlation

 

Straightforward gold standard vs new test comparison

 

Wide confidence intervals die to sample size

 

3.5% of the tests did not perform adequately

High performance of the dual POC HIV/syphilis test

 

Good comparison of gold standard HIV testing to the POC test

High
Browning

Posterior Segment Manifestations of Active Ocular Syphilis, Their Response to a Neurosyphilis Regimen of Penicillin Therapy, and the Influence of Human Immunodeficiency Virus Status on Response

Ophthalmology. 2000 Nov;107(11):2015-23

Retrospective chart review pts with ocular syphilis

 

+FTA-ABS or MHA-TP, 12/14 had a +RPR

14 pts, 5 HIV positive

 

The testing for the HIV+ pts no different than HIV- pts

Case series, not addressing HIV + vs HIV- testing comparisons Not relevant to the key question NR
Burgoyne et al

Chronic Syphilitic Polyarthritis Mimicking Systemic Lupus Erthematosus/Rheumatoid Arthritis as the Initial Presentation of Human Immunodeficiency Virus Infection

J Rheumatol. 1992 Feb;19(2):313-5

Case report HIV and chronic syphilitic polyarthrits RPR- on initial evaluation and + 5 months later ith RPR 1:128 and +FTAABS Case report

 

Does not address the key question

Prozone reraction may be higher in HIV infected individuals I
Chen et al

An unusual cause of membranous glomerulonephritis in a patient with HIV

Int Urol Nephrol (2012) 44:983-986

Case presentation HIV with Membranous GN RPR 1:256, FTA-ABS +, VDRL 1:128, CSF VDRL 1:2 Case report

 

Only addresses syphilis clinical manifestations in HIV infected male

Not relevant to the key question I
Don et al

Malignant Syphilis (Lues Maligna) and Concurrent Infection with HIV

International Journal of Dermatology, Vol 34, No 6, June 1995

Case series 6 pts in New York with leus maligna, all HIV positive All lab + for NTST and TST testing Case series addressing clinical presentation of syphilis in HIV infected pts – no lab comparisons Syphilis testing as expected for the non-HIV infected population in leus maligna I
Erbelding et al

Syphilis Serology in Human Immunodeficiency Virus Infection:  Evidence for False-Negative Fluorescent Treponemal Testing

The Journal of Infectious Diseases 1997; 176:1397-400

1988 1117 injection drug users (high risk) tested every 6 months for HIV and syphilis (RPR and FTA-ABS)

 

3 groups – syphilis -, BFP and syphilis+

 

High titer BFP (>/= 1:4) had immunoblot testing (17-kDa and 47 kDa) serially

 

No true gold (reference) standard

112 pts with BFP, 89% HIV+

pts syphilis+, 81% HIV+

 

BFP: 61% RPR 1:8 or less with persistent – FTA-ABS, 31% RPR >1:8, 4.5% eventually FTA-ABS + and 3.6% treated prior

 

Immunoblot was used to assess atypical serology results

No reference standard so used temporal patterns

 

Cannot extrapolate results to low-titer BFP pts

 

High risk pt population only

Routine serologic tests may be falsely negative in some HIV infected pts

 

FTA-ABS test-negative syphilis occurs in some HIV infected pts though hard to quantify due to limited available testing

Medium
Feraru et al

Neurosyphilis in AIDS patients:  Initial CSF VDRL may be negative

Neurology 1990; 40:541-543

2 HIV + pts with neurosyphilis Initial CSF VDRL negative though clinical sx suspicious and serology +

 

CSF protein, glucose and leukocyte abnl in both pts

2 patients so limited ability to extrapolate CSF VDRL may be negative – ? CSF FTA-ABS as a screen though false positive rate a concern

 

Other CSF markers in the setting of clinical disease warrants a diagnosis

I
Ganesan et al

A Single Dose of Benzathine Penicillin G Is as Effective as Multiple Doses of Benzathine Penicillin G for the Treatment of HIV-Infected Persons with Early Syphilis

Clin Infect Dis. 2015 Feb 15;60(4):653-60

US Military HIV natural history study with every 6 month labs Jan 1986-Aug 2013

 

Non-tST and TST confirmation

 

Assessed response to treatment at 13 months

 

350 HIV infected pts with early stage syphilis (478 cases)

 

No mention of syphilis testing sensitivities/specificites

Various TSTs used over the timespan of the study

 

Staging not well captured (“early” as within 365 days seroconversion)

 

This was a response to treatment assessment

 

No comparison to HIV negative pts

Not relevant to the key question NR
Ghanem et al

Neurosyphilis in a clinical cohort of HIV-1-infected patients

AIDS 2008, 22:1145-1151

Johns Hopkins HIV clinic

 

1990-2006 all neurosyphilis pts

-RPR/FTA-ABS serology

-CSF abnormalities

180 pts with 231 cases syphilis- 41 cases neurosyphilis

 

66% symptomatic, median RPR 1:512, CSF VDRL 50% asx and 79% sx.

Goal was to evaluate risk factors, clinical pres and follow-up.

 

This was not a lab analysis not were there HIV negative comparisons

CSF VDRL can be negative in both Sx and Asx HIV infected pts with neurosyphilis Medium
Ghanem et al

Antiretroviral Therapy is Associated with Reduced Serologic Failure Rates for Syphilis among HIV-Infected Patients

Clinical Infectious Diseases 2008;47:258-65

Retrospective cohort study HIV pts at JH 1990-2006

 

Included pts with syphilis with 2 serology available, initial and within 365 days of treatment

 

RPR and then FTA-ABS

180 HIV+ pts with syphilis, 231 cases included

 

39% serologic failure after treatment

 

16% seroreversion

Primary syphilis with NR serology excluded

 

Study focused on serologic response

 

Limited ability to answer key question using data presented

Seroreversion rates different than reported pre-PCN era ?HIV influence vs PCN usage

 

Unsure if serologic failure association

 

Serologic response may be slower

 

Does not answer the key question

NR
Ghanem et al

Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics

Sex Transm Infect 2007;83:97-101

Baltimore STD clinics 1992-2000

 

RPR, FTA-ABS

Primary syphilis with NR serology excluded

 

Serologic failure 4-fold rise in titers 30-400 days after Rx or lack 4-fold drop by 270-400 days

129 HIV + vs 168 HIV-

 

HIV+ more likely to have lower RPR titers

 

Higher likelihood serologic failures in HIV+ pts (though not clinical failure)

 

No difference in timing of response for each stage if HIV+ vs HIV-

Serologic response in HIV – vs HIV + pts Not relevant to the key question NR
Glatt et al

High-Titer Positive Nontreponemal Tests in Negative Specific Treponemal Serology in Patients with HIV Infection and/or Intravenous Substance Abuse

Journal of Acquired Immune Deficiency Syndromes 1991; 4: 861-864

Case series

 

1/90-8/90 + RPR or VDRL with titer ≥  1:16, – FTA-ABS

8 pts with data available

 

6/8 HIV+

 

Clinically no syphilis

Limited case series

 

Unknown whether False negative FTA-ABS so hard to make conclusions based on this report

High titer false positive in HIV though very limited in number I
Goldberg et al

Poor Correlation Between Reactive Syphilis Serology and Human Immunodeficiency Virus Testing Among Potential Cornea Donors

Am J Ophthalmol. 1995 Jan;119(1):1-6

Questionnaire sent to 94 eye banks

 

RPR or VDRL with MHA-TP or FTA-ABS

1% RPR or VDRL + with 61% of those confirmed (n=19)

0/19 had HIV

No syphilis pt had HIV Not relevant to the key question NR
Gourevitch et al

Effects of HIV infection on the Serologic Manifestations and Response to Treatment of Syphilis in Intravenous Drug Users

Ann Intern Med. 1993 Mar 1;118(5):350-5.

Data from 2 studies: IVDU with HIV starting in 1985 in NYC and HIV negative pts

 

Syphilis testing baseline and 6-12 mos intervals

 

ART or RPR, FTA-ABS or MHA-TP

31 HIV + with syphilis

19 HIV- with syphilis

 

2 HIV+ and 1 HIV- had +CSF VDRL

 

Non-treponemal titers higher with HIV+ only if prior h/o syphilis

 

Rate of seroreversion (FTA-ABS or MHA-TP to negative) did not differ in HIV+ or HIV- pts

Small series, old HIV testing used FTA-ABS or MHA-TP seroreversion did not differ among stage of disease or HIV status

 

HIV+ pts with prior h/o syphilis had higher non-treponemal titers

Medium
Haas et al

Sensitivity of Treponemal Tests for Detecting Prior Treated Syphilis during Human Immunodeficiency Virus Infection

Journal of Infectious Diseases 1990;162:862-866

MSM population with serum samples stored at UCSF – 2 cohorts

– 1982-1985 Sx HIV

– 1983-1984 HIV – or Asx HIV+

 

Syphilis Dx confirmed

VDRL with FTA-ABS or MHA-TP

109 pts: HIV- n=19, AIDS n=14, AIDS complex n=7 and HIV + Asx n=69

 

13 seroreverted, split MHA-Tp and FTA-ABS

 

All HIV- pts had persistently reactive trep test. 5/69 HIV+ asx, 8/21 sx HIV lost reactivity

 

HIV(-) sensitivity of trep test to ID prior syphilis 93% vs 62% in sx HIV+ pts

Well characterized pt population with complete data available.

 

Solid design, good quality data

Seroreversion of a treponemal test in HIV infected individuals is higher than HIV-

 

Treponemal tests do not reliably identify prior syphilis infection in HIV + pts, particularly if sx

 

Loss of reactivity related to immune function

High
Halperin

Neuroretinitis Due to Seronegative Syphilis Associated with Human Immunodeficiency Virus

Journal of Clinical Neuro-opthalmology 12(3): 171-172, 1992

Case report Neuroretinitis VDRL and FTA-ABS negative

CSF VDRL NR

HIV+

Improved with PCN though no confirmation that this was syphilis Not relevant to the key question NR
Hay et al

Detection of treponemal DNA in the CSF of patients with syphilis and HIV infection using the polymerase chain reaction

Genitourin Med 1990;66:428-432

3 groups:

Group 1: HIV-, no syphilis, Group 2: syphilis (TPHA and FTA+)

Group 3: HIV+ no susp syphilis

All had an LP for PCR

1/30 pts Group 1 PCR+ neonate, serology in mom and baby neg

10/19 Group 2 +PCR – 2 neurosyphilis (1 HIV+), 1 asx neurosyphilis, 7 latent syphilis

7/28 PCR positive all in pts with CNS disease

 

PCR CSF sens 59%, spec 97%, PPV 91%, NPV 83% in pts not previously treated for syphilis if HIV neg

 

PCR CSF sens 38%, spec 87%, PPV 87% and NPV 62% if HIV + for predicting h/o syphilis

 

Old study using PCR – difficult to extrapolate to current methodology HIV affects CSF PCR results – not a good predictor of previous disease Medium
Herring et al

A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera

Sex Transm Infect. 2006 Dec;82 Suppl 5:v7-12

Using archived sera, several labs independently evaluated several POC syphilis tests No HIV data Not relevant to the key question NR
Hess et al

Sensitivity and Specificity of Point-of-Care Rapid Combination Syphilis-HIV-HCV Tests

PLoS One. 2014 Nov 6;9(11):e112190

5/2011-6/2013 Long Beach, Ca STD screening

 

POC test and gold standard test

– TPPA/RPR

 

Dual Path platform(DPP) syphilis creen and confirmatory, DPP HIV-Syphilis and DPP HIV-HCV-Syphilis

948 pts – Hiv prevalence 7% and syphilis 2%

 

DPP Syphilis Screen and Confirm Sens nTr test 48%, spec 99% when compared to PRP alone, improves if TPPA positive and even higher if RPR ≥ 1:8 also

 

DPP HIV-Syphilis – 46.4% sens, 99.6% spec for syphilis, 100% for HIV for sens and spec

Stage not identified

 

Low prevalence syphilis

These multi-infection POC kits good for HIV, not syphilis testing

 

Better sensitivity for syphilis in pts with higher RPR titers

NR
Hicks et al

Seronegative Secondary Syphilis in a Patient Infected with the Human Immunodeficiency Virus (HIV) with Kaposi Sarcoma

Ann Intern Med. 1987 Oct;107(4):492-5

Case report HIV + with KS, concerns for secondary syphilis VDRL and FTA-ABS negative, dilutions remained negative

 

Biopsy skin lesion + spirochetes and eventually +VDRL and FTA-ABS over time

Only one case – secondary syphilis with initial negative testing in an immunocompromised host Negative testing in  immunocompromised host does not rule out syphilis

 

Diagnosis made on biopsy with staining

I
Hutchinson et al

Altered Clinical Presentation of Early Syphilis in Patients with Human Immunodeficiency Virus Infection

Ann Intern Med. 1994;121:94-99

Retrospective chart review

 

STD clinic in Baltimore, screening for syphilis and HIV 1/1990-11/1991

 

Syphilis taging performed

 

RPR and FTA-ABS

309 pts with early syphilis and HIV testing

– 23% seropositive for HIV, 39% of whom had previous syphilis and higher % had secondary syphilis.

This was a study evaluating risk factors, clinical presentation and response to treatment, not focusing on syphilis testing  Not relevant to the key question NR
Jinno et al

Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging Era of universal antiretroviral therapy use

BMC Infectious Diseases 2013, 13:605

Los Angeles, Ca

Retrospective chart review- HIV+ with early syphilis

5/2006-5/2011

RPR ≥ 1:4 and FTA-ABS confirmation

 

Primary outcome response to treatment

560 pts, median RPR 1:64

 

Low CD4 counts associated with serologic failure after appropriate Rx

Assessed type of syphilis treatment and serologic response, not lab testing specifically Not relevant to the key question NR
Johnson et al

Specific syphilis serological tests may become negative in HIV infection

AIDS 1991, 5:419-423

Australia – stored serum of pts with syphilis +/- “AIDS”

 

Paired samples 3 or more years between, collected 1972-1985

 

TPHA and FTA-ABS

29 paired sera AIDs+ and 29 AIDs-

 

41% AIDS + significant fall in levels of TPHA or FTA-ABS, only 14% in controls

Limited HIV data

 

Time lapse data useful – what happens over time for HIV+ vs HIV- syphilis serology

 

RPR not re-assessed for this study

In HIV+ pts, serologic evidence of past infection may disappear High
Kastner et al

Syphilitic Osteitis in a Patient with Secondary Syphilis and Concurrent Human Immunodeficiency Virus Infection

Clinical Infectious Diseases 994; 18:250-2

Case report secondary syphilis and HIV No testing information Not relevant to the key question NR
Kuo et al

Vitritis as the Primary Manifestation of Ocular Syphilis in Patients with HIV Infection

Ann Intern Med. 1987 Oct;107(4):492-5

3 cases HIV positive with ocular syphilis Case 1: RPR and TPHA +

CSF VDRL +

Case 2: RPR and TPHA+, CSF VDRL+

Case 3: RPR and TPHA +, VDRL +

Very limited case series, old testing CSF pleocytosis not a good measure for neurosyphilis as increases also in some pts with HIV

 

 

I
Lee SY et al. Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection. J Ophthalmic Inflamm Infect, 2015; 5(1): 56.

 

Retrospective cohort study of patients with ocular syphilis from 1/1/2008-4/30/2014 at the Los Angeles County Medical Center

29 eyes of 16 consecutive patients (10 HIV-positive and 6 HIV-negative) were included

All patients were positive for both the RPR and FTA-ABS serology tests

All patients were males

Regardless of HIV status, CSF exam was frequently abnormal: positive CSF-FTA or VDRL test results in 7 patients or either elevated CSF WBC count or elevated CSF protein in 6 patients.

Retrospective cohort study. Therefore, difficult to infer causality. The presence of HIV significantly increases serum RPR titers in patients with ocular syphilis compared to those without ocular syphilis.

 

Medium
Leon SR et al. Laboratory Evaluation of a Dual-Path Platform Assay for Rapid Point-of-Care HIV and Syphilis Testing. J Clin Microbiol. 2016; 54(2): 492-4

 

Prospective cohort study

Serum specimens were collected between 2013-2014 from MSM and transwomen who had been recruited into an ongoing cohort study in Lima, Peru

450 specimens were analyzed.

Of the 450 specimens, 100 were confirmed by Western blotting to be HIV-1 positive only, 99 were positive for Treponema pallidum antibodies by TPPA testing only & 51 were positive for both HIV and Treponema pallidum antibodies by Western blotting and TPPA testing.

The sensitivity of the HIV antibody component was 100% & the specificity was 98.7%.

Study characterized the use of a single-use, visual and qualitative immunochromatographic, dual rapid test for the detection of antibodies to HIV types 1 and 2 and Treponema pallidum in human serum, plasma, or venous samples.

Limitations – Limited external validity (study on only people from Peru); the population had high risks for HIV and syphilis acquisition; therefore, values for the sensitivity and specificity of the test might not be representative.

The sensitivity and specificity of the Chembio DPP HIV-syphilis rapid test to detect HIV antibodies in the presence of HIV-syphilis co-infection is 100%. High
Malone JL et al. Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy. Am J Med. 1995; 99(1): 55-63.

 

Retrospective cohort study between 10/1985-03/1991.

100 HIV-infected adults with syphilis evaluated at a Naval Medical Center tertiary-care military HIV program

Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis.

Serologic or clinical relapse occurred in 10 of the 56 treated patients (17.9%)

7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy

Retrospective cohort study. Therefore, it is very difficult to infer causality. Standard penicillin regimens, including high-dose intravenous penicillin are inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Medium
Marra CM et al. Neurocognitive impairment in HIV-infected individuals with previous syphilis. Int J STD AIDS. 2013; 24(5): 351-5

 

Non-nested case controlled study

82 of 1574 enrollees in CHARTER, a prospective, observational study

These cases were matched to 84 controls by age (+2 years), gender, ethnicity and HIV risk factor.

Sera from 101 of 166 participants were FTA-ABS reactive, indicating past or current syphilis.

 

Non nested case control study with its limitations

Historical information on syphilis is not collected prospectively, and was based on self-report.

No information on previous syphilis stage or specific treatment

Number of subjects with neuro-syphilis was small.

HIV-infected patients with past syphilis (negative RPR, positive FTA) performed more poorly on a comprehensive neuropsychological test battery than HIV-infected patients who had never had syphilis. NR
Marra CM et al. Reduced Treponema pallidum-Specific Opsonic Antibody Activity in HIV-Infected Patients With Syphilis. J Infect Dis. 2016, 15; 213(8): 1348-54.

 

Study of CSF abnormalities in syphilis conducted in Seattle, Washington, from 07/2001-12/2013

235 individuals were included (72%of participants had early syphilis, & 28% had late latent syphilis or syphilis of unknown duration

Opsonic activity was higher with higher serum RPR titers (P < .001), and in those treated for uncomplicated syphilis before serum collection (P < .001).

Opsonic activity was lower in HIV-infected than in HIV-uninfected individuals even after the above factors were taken into account (P = .006).

Although differences in serum opsonic activity in HIV-infected versus HIV-uninfected were measured, it is difficult to determine whether these differences reflect lower concentration of antibody, diminished antibody binding, responses to different antigen repertoires, or some other factor Serum T. pallidum-specific opsonic activity is significantly lower in HIV-infected individuals. Medium
Marra CM et al. Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected individuals. Neurology 2004, 13; 63(1): 85-8.

 

Retrospective cohort study at Harborview medical Centre, Seattle Washington between 1/28/2002-04/24/2003.

There were 47 cases: 35 subjects had early syphilis: 2 with primary, 25 with secondary, and 8 with early latent syphilis.

CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of neurosyphilis.

Elevated % CSF B cells in fresh and cryopreserved samples were specific (100%) but not sensitive (40 and 43%) in post hoc analyses.

There was an inherent limitation of the sensitivity/specificity of this diagnostic test for neurosyphilis in the absence of a true gold standard. When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of neurosyphilis. Medium
McMillan A et al. Influence of human immunodeficiency virus infection on treponemal serology, in patients who have been treated for syphilis. J Infect. 1990; 21(1): 95-103.

 

20 patients with HIV-syphilis co-infection who were recruited at the Edinburgh University in Scotland.

All cases were previously treated for syphilis.

VDRL, TPHA and FTA testing were done.

The Captia Syphilis M test (M Diagnostics) was used for the detection of serum antitreponemal IgM

Serum immunoglobulins detected using radial immunodiffusion & flow cytofluorimetry

This is a case series of 20 patients; hence, there is limitation in the sample size of the study to make definitive conclusions. In HIV/Syphilis co-infection, serological data fails to show recrudescence. Medium
Musher DM et al. Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. Ann Intern Med. 1990, 1; 113(11): 872-81.

 

Systematic review of studies (1971-1990) on early neurosyphilis and HIV co-infection.

38 patients were included in the study

In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared

Sixteen had previously been treated for syphilis, of which 5 (31%) had received benzathine penicillin within the previous 6 months.

There was no detailed explanation of the methods for data extraction in the included studies Skin lesions and VDRL antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy Medium
Oboho IK et al. The impact of combined antiretroviral therapy (cART) on biologic false-positive rapid plasma reagin serologies in a longitudinal cohort of HIV-infected persons. Clin Infect Dis. 2013; 57(8): 1197-202.

 

Nested case controlled study of 711 HIV-infected patients enrolled in the Johns Hopkins HIV Clinical Cohort. Of 711 patients with HIV, 96 (13.5%) had BFP tests and 342 (48.1%) had syphilis.

20 of 96 (23%) had persistent biologic false-positive (BFP) tests.

cART use was also associated with decreased odds of BFP persistence

The high prevalence of concurrent risk factors for BFPs such as viral hepatitis and intravenous drug use makes it difficult to ascertain the relative contribution of a single factor to BFP occurrence. The use of cART appears to decrease the odds of BFP RPR tests. This finding suggests that non-treponemal titer fluctuations in persons with HIV may reflect the influence of factors unrelated to syphilis disease activity. High
Rolfs RT et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med. 1997, 31; 337(5): 307-14.

 

Multicenter, randomized, double blind trial of 2 treatments for early syphilis in HIV infected patients.

541 patients were treated from 1991-1994.

Rates of treatment failure did not differ according to treatment group (18% versus 17%) to usual therapy versus enhanced therapy respectively

 

Multicenter randomized controlled trial, which is the gold standard for interventions in clinical medicine.

Limitations – It was difficult to rule out infrequent occurrence of serious adverse clinical outcomes in HIV-infected patients after treatment for syphilis.

A second concern was the suboptimal rate of follow-up, which may have allowed some serious sequelae to go undetected

After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. High
Seña AC et al. Predictors of serological cure and Serofast State after treatment in HIV-negative persons with early syphilis. Clin Infect Dis. 2011; 53(11): 1092-9

 

Open-labeled RCT of 465 patients between 6/12/00-03/06/09 at 5 STD clinics in North America and 3 clinics in Madagascar

The primary outcome was response to therapy, determined on the basis of changes in RPR titers at 6 months after treatment

Serological cure was associated with younger age, fewer sex partners, higher baseline RPR titers, and earlier syphilis stage (P ≤ .008).

There was a less significant association with Jarisch-Herxheimer reaction after treatment (P = .08).

The analyses was limited because all participants who had a change in protocol status or were serofast at the 6-month evaluation were retreated with benzathine penicillin Serological cure at 6 months after early syphilis treatment is associated with age, number of sex partners, Jarisch-Herxheimer reaction, and an interaction between syphilis stage and baseline RPR titer. NR
Smith G et al. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med J. 2004; 97(4): 379-82.

 

Case report describing the prozone phenomenon (false negative response resulting from overwhelming antibody titers which interfere with the proper formation of the antigen-antibody lattice network necessary to visualize a positive flocculation test). A 21-year-old homosexual man presented with fevers to 103°F, chills, nausea, vomiting, serum

RPR was negative, but when diluted at 1:4 became positive and remained so to a dilution of greater than 1:2,056.

Single case report of prozone phenomenon. Hence, there is lack of generalizability, no possibility to establish cause-effect relationship & danger of over-interpretation This prozone effect in syphilis testing can be expected in cases of disproportionately high antibody titers, such as secondary syphilis, or with human immunodeficiency virus (HIV) coinfection I
 

Telzak EE et al. Syphilis treatment response in HIV-infected individuals. AIDS. 1991; 5(5): 591-5.

 

Non nested case controlled study at 11 STD clinics in New-York city from 06/1987-07/1988 with frozen sera

Paired sera of 338 patients with secondary syphilis

HIV-infected patients with primary syphilis when compared with HIV-negative controls were less likely to have a fourfold or greater RPR decrease or seroreversion within 6 months of treatment Non nested case control study with its inherent problems HIV may alter the RPR response High
Tomberlin MG et al. Evaluation of neurosyphilis in human immunodeficiency virus-infected individuals. Clin Infect Dis. 1994; 18(3): 288-94.

 

Study examined the use of the Treponema pallidum hemagglutination (TPHA) index and quantitative tests of CSF by means of microhemagglutination-T. pallidum for diagnosis of neurosyphilis in 58 HIV-infected persons with latent syphilis who had not recently received therapy for syphilis Five patients (9%) had reactive CSF VDRL tests and thus had proven neurosyphilis.

In 13 patients (22%), CSF findings were normal and revealed no evidence of neurosyphilis.

In 40 patients (69%), abnormal CSF findings were characteristic of neurosyphilis, but their CSF VDRL tests were nonreactive.

The difficulties in the diagnosing asymptomatic syphilis in HIV infected individuals could have affected study results. With use of the TPHA index, patients with CSF abnormalities can be better classified in regard to their need for therapy for neurosyphilis. Medium
Weissman S et al. Syphilis treatment and outcomes in HIV positive patients: Does lumbar puncture make a difference? J Clin Outcome Management 2010, 17(10): 443-7 Retrospective cohort study of HIV positive patients seen at hospital of St Raphel between 1/1/97-12/31/08 with a positive RPR or VDRL.

28 cases were included

LP was performed in 10 cases (35.7%)

Treatment success was 80% & 82% for LP groups & no LP groups respectively

5 Patients failed therapy

The retrospective nature and small sample size precludes strong correlations.

Many cases were excluded from the analysis because of a low initial treponemal titer

Lumbar puncture in HIV patients without clinical symptoms of neurosyphilis did not affect treatment success. Medium
Yinnon AM et al. Serologic response to treatment of syphilis in patients with HIV infection. Arch Intern Med. 1996; 156(3): 321-5.

 

Non nested case controlled study

64 HIV-seropositive patients with syphilis were matched with 64 patients with syphilis who were HIV negative

There were 26 matched patients with early syphilis, 26 matched patients with late syphilis, and 12 matched patients with biological false-positive RPR

All 16 patients with symptomatic syphilis were cured.

No patient developed clinical signs of neurosyphilis during the 12-month follow-up period.

29 (56%) of 52 HIV-positive patients with early or late syphilis did not have a 4-fold decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52 matched controls (P = .06).

Retrospective study

Syphilis is a notoriously heterogenous disease, so it is exceedingly difficult to create perfectly matched controls.

Follow up was longer for the HIV group compared to those who were HIV negative. This may have affected the results of this study

Patients with syphilis who are HIV positive are less likely to experience serologic improvement after recommended therapy than are patients with syphilis who are HIV negative. Medium
Land AM.  Widening the differential for brain masses in human immunodeficiency virus-positive patients: syphilitic cerebral gummata. Am J Med Sci, 2013; 346(3): 253-5. Case report of a 39 year old man with a rare CNS presentation due to syphilitic cerebral gummata Case report on a man.  There was no description of how syphilis lab tests performed differently in HIV infected compared to HIV uninfected I
Navrazhina K et al. Papulonodular Secondary Syphilis Presenting as Multiple Distinct Cutaneous Lesions in an HIV-Positive Transgender Woman. Case Rep Dermatol. 2017, 29; 9(1):90-4.

 

Case report of a 51 year old transgender woman with a rare dermatologic presentation due to syphilis/HIV co-infection (papulonodular multiple skin lesions). Case report on a 51-year-old transgender woman.  There was no description of how syphilis lab tests performed differently in HIV infected compared to HIV uninfected NR
Rompalo AM et al. Association of biologic false-positive reactions for syphilis with human immunodeficiency virus infection. J Infect Dis. 1992; 165(6):1124-6. The study assessed the relationships between biologic false-positive (BFP) reactions and HIV infection. This study did not offer any new information on how syphilis laboratrory tests performed differently in HIV infected compared to HIV uninfected NR
Rompalo AM et al. Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study. Sex Transm Dis. 2001; 28(3):158-65.

 

A prospective, multicenter, randomized, controlled trial of enhanced versus standard therapy to compare the benefit of enhanced therapy, the clinical importance of central nervous system involvement, and the clinical manifestations of early syphilis infection among HIV-infected and HIV-uninfected patients Laboratory testing did not perform differently between HIV positive and HIV negative women.  Overall, HIV infection had a small effect on the clinical manifestations of primary and secondary syphilis Medium
Rusnak JM et al. False-positive rapid plasma reagin tests in human immunodeficiency virus infection and relationship to anti-cardiolipin antibody and serum immunoglobulin levels. J Infect Dis. 1994; 169(6):1356-9.

 

Review of 3371 periodic syphilis serology results from 1077 HIV-seropositive patients in the United States Air Force HIV Natural History Study between January 1986 and June 1992 There was no difference in the incidence of biologic false-positive rapid plasma reagin (RPR) tests between HIV positive and HIV negative patients. NR
Smith NH et al. Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS. 2004; 15(5):328-32.

 

Prospective pilot study evaluating the response of HIV-infected patients with asymptomatic syphilis to one of two intensive antibiotic treatment regimens (ceftriaxone or procaine penicillin (plus oral probenecid). There was no difference in the serologic response to daily treatment with ceftriaxone vs that with procaine penicillin plus probenecid; both treatments were associated with comparatively high rates of serological non-response and relapse in both HIV infected and non-infected patients. NR
Smith JL et al. Syphiloma/gumma of the optic nerve and human immunodeficiency virus seropositivity. J Clin Neuroophthalmol. 1990; 10(3):175-84.

 

Case report of a 68 year old man with a rare CNS presentation of syphilis (syphiloma/gumma of the optic nerve). Case report on a man. There was no description of how syphilis lab tests performed differently in HIV infected compared to HIV uninfected. I
Smith ME et al. Otologic manifestations of AIDS: the otosyphilis connection. Laryngoscope. 1989; 99(4):365-72.

 

Case series of 5 cases of otosyphilis presenting in patients with HIV infection Study showed that HIV may alter its course and hasten the development of otosyphilis. However, there was no description of how syphilis lab tests performed differently in HIV infected compared to HIV uninfected I
Sperling RS et al. HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis. Mt Sinai J Med. 1992; 59(1):67-8.

 

This was just a descriptive study: describes HIV-1 seroprevalence in pregnant women testing positive on serologic screening for syphilis. There was no description of how syphilis lab tests performed differently in HIV infected compared to HIV uninfected NR
See comment in PubMed Commons belowTerry PM et al. Are serological tests of value in diagnosing and monitoring response to treatment of syphilis in patients infected with human immunodeficiency virus? Genitourin Med. 1988; 64(4):219-22.

 

This study assessed the value of serological tests in diagnosing and monitoring the response to treatment of syphilis in patients infected with HIV In all the patients, the serological responses to infection and after treatment were consistent with the experience of syphilis in HIV seronegative patients. The tests did not differ in performance in HIV compared to non HIV patients. NR