Audit of Syphilis Screening in Pregnancy

Audit of Syphilis Screening in Pregnancy Tables Table 1:Syphilis confirmatory test results for forty nine  pregnant woman 18 Table 2:Syphilis screening results of eleven new-borns of  positive syphilis mother 24 Table 3: Positive syphilis confirmatory test results for sixteen  pregnant woman 30 Figures Figure 1: The laboratory turnaround time of syphilis screening  for mothers 28 Figure 2: The laboratory turnaround time of syphilis screening  for new-borns 28 Tables Table 1: Syphilis confirmatory test results for forty nine pregnant woman 18 Table 2: Syphilis screening results of eleven new-borns of positive syphilis mothers 24 Table 3: Positive syphilis confirmatory test results for sixteen pregnant woman 30 Figures Figure 1: The laboratory turnaround time of syphilis screening for mothers Figure 2: The laboratory turnaround time of syphilis screening for new-borns ABSTRACT Objective: A re-audit of syphilis screening in pregnancy was carried out to ensure that the improvements in laboratory and clinical aspects of management for the antenatalof pregnant women with positive syphilis screening and their new-born babies fully met were in accordance with the UK National Guidelines on the Management of Syphilis (Kingston et al., 2008) and the Guidelines for the Management of Syphilis in Pregnancy and the Neonatal Period (Stringer et al., 2013). Methods: Patients’ data were collected via query of the three databases: Clinisys Labcentre, Telepath and EuroKing. The n the data were analysed using Microsoft Access 2013. Results: Samples from Forty nine49 pregnant woman with positive syphilis results serology were referred to a reference laboratory laboratory were sent to MRI for syphilis serological confirmatory testing. Sixteen pregnant woman with of these women were confirmed to have had had positive syphilis were identified. Ten pregnant woman were re-tested screened at least twice during their pregnancy and six pregnant woman were only screened tested once during pregnancy. Over-testing of for treponemal IgM were seen in nineteen patients[h1] with non-reactive RPR titre. Only eleven babies born to mothers with syphilis were followed-up with serial serological tests for syphilis. Only four new-borns were fully screened. Some of the new-borns were not tested with treponemal IgM due to sample insufficiency. Conclusion: There were some improvements seen since the first audit which includes the changes of the confirmatory testing schedule in MRI, lower screening false positive rate, and increased follow-up of the new-borns. There were also things to improve in the management of syphilis in pregnancy and the new-borns of positive syphilis mothers. Treponemal IgM test should be performed only when the RPR test were reactive to prevent over-testing of patients. The test algorithm for screening of syphilis in new-borns should give priority to RPR test and treponemal IgM to prevent under-testing[h2]. In-house confirmatory testing should be considered to allow reduction of test turnaround time’s thereby aiding patient management.Improvements[h3] should be made in the management of syphilis in pregnancy and the new-borns of positive syphilis mothers. Treponemal IgM test should be performed only when the RPR test were reactive to prevent over-testing of patients. The test algorithm for screening of sy philis in new-borns should give priority to RPR test and treponemal IgM to prevent under-testing[h4]. 1.0  INTRODUCTION 1.1  Syphilis Syphilis is an infectious disease caused by Treponema pallidum (T.pallidum) subspecies pallidum. The disease is transmitted from human to human, and humans are its only known natural host (Woods 2005). Epidemiologically, in the UK, cases of syphilis have increased in England since 1997 led by a series of outbreaks reported from Manchester, London and Brighton (Health Protection Agency 2009). Since 1999, diagnoses of infectious syphilis have been made in heterosexuals where the outbreaks are linked to sex work, students and young people. But, there was a changing pattern of infection between 1999 and 2008, when seventy three percent of new diagnoses of infectious syphilis were reported in men who have sex with men (Health Protection Agency 2009). The transmission is primarily by sexual activity (Zeltser Kurban 2004) (vaginal and anal intercourse) and by direct contact with active primary or secondary lesions (Lafond Lukehart 2006) for example through oral sex and kissing at or near an infectious lesion (Kent Romanelli 2008). T.pallidum may invade the host through normal mucosal membranes and also through minor abrasions in the skin (Zeltser Kurban 2004) such as from sexual trauma, causing an inflammation, ulcer and then spreading through the blood stream to other parts of the body (Goh 2005). 1.2  Syphilis in Pregnancy Mothers with untreated syphilis may seriously complicate their pregnancy. Vertical transmission of T.pallidum across the placenta (Singh Romanowski 1999) can occur at any time during pregnancy (Vaules et al., 2000; Oswal Lyons 2008), this leads to wide dissemination of the spirochete in the fetus (Woods 2005). Fetal infection resulting in spontaneous abortion, still-birth, premature delivery, non-immune hydrops fetalis and also congenital infection (Singh Romanowski 1999; Vaules et al., 2000; Ledger 2000). Vertical transmission may occur at any stage of syphilis infection. However, the transmission is more common in mothers with primary and secondary stage of syphilis (Singh Romanowski 1999; Vaules et al., 2000; Oswal Lyons 2008) as the risk of transmission depends on the levels of spirochaetemia which are higher in these stages compared to other stages (Vaules et al., 2000). Syphilis may also be transmitted during birth by contact of the new born with the mother’s genita l lesion (Ledger 2000; Berman 2004). 1.3  Congenital Syphilis Signs of infection for early congenital syphilis may appear within the first two years of the infant’s life with clinical manifestations include hepatosplenomegaly, rash, fever, and signs of neurosyphilis, especially bulging fontanel, seizures, and cranial nerve palsies (Mattei et al., 2012; De Santis et al., 2012). As for late congenital syphilis, the sign of infection may only be seen over the first two decades with clinical manifestations such as frontal bossing, nasal cartilage destruction, and dental abnormalities (Mattei et al., 2012; De Santis et al., 2012). Congenital syphilis leads to multiple organ infection because of the widespread haematogenous dissemination (De Santis et al., 2012) that will further cause death in the fetus or new born. However, the disease is almost preventable if mothers with syphilis are treated early in pregnancy (Walker Walker 2007). 1.4  Serologic Test Diagnosis of syphilis is made based on clinical signs and symptoms, microscopic examination and serologic tests (Little 2005). Two types of serologic testing were available; non-treponemal specific tests and treponemal specific tests (Clyne Jerrard 2000). Non-treponemal tests are widely used for testing and screening for syphilis as they are rapid, simple and inexpensive (Ratnam 2005). The example of  non-treponemal tests include the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test (Kent Romanelli 2008). Due to the rate of false-positive results which present in about one to two percent for these tests, the positive results have to be confirmed by sets of treponemal-specific tests such as the T.pallidum particle agglutination (TPPA) test, T.pallidum haemagglutination (TPHA) test and treponemal enzyme immunoassay (EIA) test (Kent Romanelli 2008). 1.4.1  Antenatal Screening The detection and treatment of infectious syphilis are extremely important in preventing congenital syphilis (Chakraborty Luck 2007; Simms Broutet 2008). An effective antenatal screening programme can have a huge impact in the way of managing both mother and baby. All pregnant women should be screened for syphilis at their first antenatal appointment (French et al., 2009) and the test should be repeated early in the third trimester (Goh Thornton 2007). Also, all infants born to seropositive mothers should be examined at birth and at monthly intervals for three months until it is confirmed that serological tests are and remain negative (Oswal Lyons 2008). The primary screening tests recommended (Kingston et al., 2008) are either treponemal EIA or TPPA/TPHA. If the screening test is positive, it must be confirmed by either one of the opposite tests. VDRL or RPR will be performed when the confirmatory test gives positive results (Kingston et al., 2008). 1.5  Audit on Diagnostics of Syphilis in Pregnancy The diagnosis of infectious syphilis in women in the UK increased between 1999 and 2007. The increase of syphilis cases in women has also led to the re-emergence of congenital syphilis in the UK which may suggest sub-optimal management of patients with syphilis (Health Protection Agency 2009). In 2011, an audit on diagnosis of syphilis in pregnancy was performed at the Pennine Acute NHS Trust (PAHT) to ensure the syphilis screening in pregnant women and also the serological diagnostic of their new-born babies followed the UK standard for Microbiology Investigations in Serological Diagnosis of Syphilis which were introduced by Public Health England in 2007 (Public Health England 2014b). The purpose of introducing the standard was to assure equivalence in the investigation strategies in different laboratories across the UK (Public Health England 2014b). The audit reveals the concerns about the delays in syphilis confirmations and insufficient follow-up for new-borns of positive syphilis mothers. At least eighteen percent of positive syphilis cases took more than one month for confirmation and the turnaround time for eleven percent of the syphilis screening cases out of forty five cases took more than one week. It is also found that there was inconsistency in performing treponemal IgM test where fifty three percent of cases (twenty four cases out of forty five cases) were not tested for treponemal IgM. For the management of neonates, only four new-borns were followed-up and among four new-borns, only one have been followed up according to the guidelines. Recommendations made from the audit includes the improvement of time to confirmation of specimens, changes of confirmation test by using treponemal IgM to all pregnant woman, referral of all pregnant woman with inconclusive syphilis confirmation to Genitourinary Medicine (GUM) clinic and management of new-borns where follow-up should be completed according to the guidelines provided (Vladana et al., 2011). 1.6  Re-audit of Syphilis Screening in Pregnancy A re-audit of syphilis screening in pregnancy at the PAHT was performed to discover if changes made after the first audit recommendations have led to the improvement of services. The re-audit was carried out three years after the first audit done in 2011. The re-audit aimed to ensure that the improvements in laboratory and clinical aspects of management for the antenatal women with positive syphilis screening and their new-born babies were in accordance with the UK National Guidelines on the Management of Syphilis (Kingston et al., 2008) and the Guidelines for the Management of Syphilis in Pregnancy and the Neonatal Period (Stringer et al., 2013). 2.0  METHODOLOGY 2.1  Background The PAHT comprises four major district general hospitals; North Manchester General, Fairfield General Hospital, Rochdale Infirmary and The Royal Oldham. Some 12,000 women annually present for antenatal care. Women usually attend for antenatal care at one of three antenatal clinics or one of several General Practice Clinics within the community. In the UK antenatal infectious disease screening is usually performed at three months gestation (http://www.screening.nhs.uk/). Women are offered screening for rubella immunity, hepatitis B virus infection, human immunodeficiency virus infection and T.pallidum (syphilis) infection. Among 12,000 women screened within the PAHT in the period 1st January 2013 to 31st December 2013, a series of forty nine pregnant woman with positive syphilis serology were identified. To determine whether syphilis screening and follow up care of babies born to these mothers followed the UK Guidelines of the Management of Syphilis (Kingston et al., 2008) and the Gui delines for the Management of Syphilis in Pregnancy and the Neonatal Period (Stringer et al., 2013), a retrospective study was performed. 2.2  Diagnosis of Syphilis Pathway Patients’ blood sample was collected with informed consent at the antenatal clinic and laboratory test requests were made. The patients’ information was recorded in the maternity information system database; â€Å"EuroKing† (Euroking, Chertsey, Surrey, UK). Samples were transported to The Royal Oldham Hospital (TROH) microbiology laboratory via the hospital transport system to be tested. Patient demographic information was recorded in the laboratory data system Clinisys Labcentre (Clinisys, Chertsey, Surrey, UK). If the syphilis screening test was negative, a report was generated and then posted to the antenatal clinics where the sample came from. If the syphilis screening test was positive, the sample was sent to a reference laboratory, Manchester Medical Microbiology Partnership Laboratory at Manchester Royal Infirmary (MRI) for confirmatory testing. Testing at the MRI comprises two treponemal enzyme immunoassay tests for total treponemal antibody; a T.pallidum specific assay (EIA); the T.pallidum particle agglutination assay (TPPA); the reagin precipitin assay (RPR) and where appropriate a T.pallidum specific IgM enzyme immunoassay (IgM) in accordance with national guidelines (Kingston et al., 2008). These results were recorded in the MRI laboratory database system, (Telepath; CSC Healthcare, Banbury, Oxfordshire, UK) and a printed copy of the patient test results was sent back to TROH microbiology laboratory. The reference laboratory report was transcribed onto the Clinisys Labcentre system and a printed report was generated to be to the antenatal clinics. Finally, the patients’ report received by the antenatal clinics was recorded in the patients’ notes and updated in the EuroKing system. 2.3  Data Collection Data collection for the study was accomplished via query of the three databases: the PAHT laboratory database system, Clinisys Labcentre, the MRI database system, Telepath and the maternity information system database, EuroKing. The data gathered including the patients’ hospital number, NHS number and specimen number, date of birth, the date of sample collection and report, and also the syphilis serology data which includes the patients’ treponemal EIA, TPPA, RPR and treponemal IgM results. The sample collection and sample reported data were obtained to investigate the turnaround time taken for the diagnosis within the laboratory. 2.4  Analysis of Data The laboratory system data was presented as Microsoft Excel spreadsheets (Microsoft Corporation, Seattle, USA). All the patients’ data were then imported and assembled in Microsoft Access 2013 (Microsoft Corporation, Seattle, USA). The data for the forty nine pregnant woman with positive syphilis serology were analysed using Microsoft Access 2013 (Microsoft Corporation, Seattle, USA). 2.5  Clinical Audit This was conducted under the Clinical Audit provision of the NHS National Research Ethics Committee (National Research Ethics Service 2008). The work was registered and approved as a Clinical Audit with the Clinical Audit Department of the PAHT. Data analysed was anonymised before release from the Trust to comply with Data Protection Guidelines (Caldicott Committee 1997). The clinical audit used the UK National Guidelines on the Management of Syphilis (Kingston et al., 2008) as a standard. 3.0  RESULTS Fifty positive syphilis serology results were identified from forty nine pregnant woman undergoing routine antenatal infectious disease screening at TROH microbiology laboratory. All specimens were screened with Chemiluminescent Microparticle Immunoassay test using the Abbott Architect Syphilis TP Assay (Abbott Diagnostics, Chicago, USA). The fifty specimens were also sent to the Manchester Medical Microbiology Partnership Laboratory, MRI which acts as a reference laboratory for syphilis serological confirmatory testing. 3.1  Confirmation Methods by MRI The reference laboratory confirms syphilis screening with two treponemal EIAs, a semi-quantitative TPPA, a semi-quantitative RPR, and where appropriate a T.pallidum specific EIA for IgM antibody in accordance with national guidelines (Kingston et al. 2008). The first treponemal EIA test was the same Abbott Architect Syphilis TP Assay (Abbott Diagnostics, Chicago, USA) used at TROH for syphilis serological testing; the second treponemal EIA test used the DiaSorin Liaison XL System (DiaSorin S.p.A, Saluggia, Italy), the semi-quantitative TPPA was the Serodia TPPA Assay (Fujirebio Diagnostics, Inc., Tokyo, Japan), the semi-quantitative RPR was the Abbott Syfacard – RR card test (Abbott Diagnostics, Chicago, USA), and the T.pallidum specific EIA for IgM were run using CAPTIA Syphilis-IgM Assay (Trinity Biotech, Ireland, UK). Where necessary, further testing using T.pallidum specific immunoblotting and/or T.pallidum specific polymerase chain reaction testing are also used in confir mation testing. All specimens were confirmed using treponemal EIA, TPPA and RPR but only about twenty nine specimen out of fifty specimen were tested using treponemal IgM. There were seventeen positive screening with syphilis and thirty three negative screening with syphilis. Negative screening was defined by having negative results for either one or both treponemal EIA, TPPA titres of less than 1:80 and RPR titre of less than 1:2; positive results were defined by having positive results for both treponemal EIAs, a TPPA titre of greater than or equal to 1:160, RPR titre greater than or equal to 1:2 and positive results of treponemal IgM (Table 1). Table 1: Syphilis confirmatory test results for forty nine pregnant woman. Patient numbers with symbol â€Å"*† are pregnant woman with positive syphilis results. Patient Test TEIA1 TEIA2 TPPA RPR IgM EIA InterpretationResult 1 1 Positive Negative Negative Negative Not Done Negative *2 1 Positive Positive 1:640 Negative Not Done Positive 2 Positive Positive 1:320 Negative Negative 3 1 Positive Negative Negative Negative Not Done Negative 4 1 Positive Negative Negative Negative Not Done Negative *5 1 Positive Positive 1:5120 1:64 Not Done Positive 2 Positive Positive 1:5120 1:64 Not Done 3 Positive Positive 1:2560 1:8 Not Done Patient Test TEIA1 TEIA2 TPPA RPR IgM EIA Result 6 1 Positive Negative Negative Negative Negative Negative *7 1 Positive Positive 1:640 Negative Not Done Positive *8 1 Positive Positive 1:1280 Negative Not Done Positive 2 Positive Positive 1:2560 1:1 Not Done 9 1 Negative Negative Negative Negative Not Done Negative 10 1 Positive Negative Negative Negative Negative Negative 11 1 Positive Negative Negative Negative Not Done Negative 2 Positive Negative Negative Negative Not Done *12 1 Positive Positive 1:5120 1:4 Negative Positive 2 Positive Positive 1:5120 1:4 Not Done Patient Test TEIA1 TEIA2 TPPA RPR IgM EIA Interpretation *13 1 Positive Positive 1:640 1:64 Not Done Positive 14 1 Positive Negative Negative Negative Negative Negative 15 1 Positive Negative Negative Negative Not Done Negative 16 1 Positive Negative Negative Negative Not Done Negative 17 1 Positive Negative Negative Negative Negative Negative 18 1 Positive Negative Negative Negative Not Done Negative 2 Positive Negative Negative Negative Not Done *19 1 Positive Positive 1:640 Negative Not Done Positive 2 Positive Positive 1:1280 Negative Not Done 20 1 Positive Negative Negative Negative Not Done Negative Patient Test TEIA1 TEIA2 TPPA RPR IgM EIA Result 21 1 Positive Negative Negative Negative Not Done Negative *22 1 Positive Positive 1:640 1:4 Not Done Positive 2 Positive Positive 1:1280 1:4 Not Done 23 1 Positive Negative Negative Negative Not Done Negative 24 1 Positive Negative Negative Negative Not Done