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      A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis

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          Abstract

          Background

          Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality.

          Objectives

          To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use.

          Design

          Systematic review and meta-analysis.

          Data sources

          We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis.

          Review methods

          We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias.

          Results

          Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs.

          Conclusion

          The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis.

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          Most cited references41

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          Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy.

          To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.
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            The effect of storage time and freeze-thaw cycles on the stability of serum samples

            Introduction: Optimal storage of serum specimens in central laboratories for a long period for multicenter reference interval studies, or epidemiologic studies remains to be determined. We aimed to examine the analytical stability of chemistry analytes following numerous freeze-thaw and long term storage. Materials and methods: Serum samples were obtained from 15 patients. Following baseline measurement, sera of each subject were aliquoted and stored at −20 °C for two experiments. A group of sera were kept frozen for up to 1, 2 and 3 months and then analyzed for stability. The other experiment consisted of one to ten times of freeze and thaw cycles. Total of 17 chemistry analytes were assayed at each time point. The results were compared with those obtained from the initial analysis of fresh samples. Median or mean changes from baseline (T0) concentrations were evaluated both statistically and clinically according to the desirable bias. Results: Of the analytes studied, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), gamma-glutamyl transferase (GGT), direct bilirubin, glucose, creatinine, cholesterol, triglycerides, high density lipoprotein (HDL) were stable in all conditions. Blood urea nitrogen (BUN), uric acid, total protein, albumin, total bilirubin, calcium, lactate dehydrogenase (LD) were changed significantly (P < 0.005). Conclusions: As a result, common clinical chemistry analytes, with considering the variability of unstable analytes, showed adequote stability after 3 months of storage in sera at −20 °C, or up to ten times of freeze-thaw cycle. All the same, such analysis can only be performed for exceptional cases, and this should be taken into account while planning studies.
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              Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi.

              To determine the association between maternal syphilis and HIV mother-to-child transmission (MTCT). Prospective cohort study. Pregnant women admitted at Queen Elizabeth Central Hospital (Malawi) in late third trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid plasma regain test and Treponema pallidum hemagglutination assay). HIV-infected women and their infants received nevirapine, according to the HIVNET 012 protocol. They were followed up at 6 and 12 weeks postpartum. Infant HIV infection was diagnosed by DNA PCR. Of the 1155 HIV-infected women enrolled, 1147 had syphilis test results, of whom 92 (8.0%) were infected. Only 751 HIV-positive women delivered live singleton infants who were tested for HIV at birth. Of these, 65 (8.7%) were HIV-infected, suggesting in utero (IU) HIV MTCT. Of the 686 infants who were HIV-negative at birth, 507 were successfully followed up. Of these, 89 (17.6%) became HIV-infected, suggesting intrapartum/postpartum (IP/PP) HIV MTCT. Maternal syphilis was associated with IU HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth weight (LBW) [adjusted relative risk (ARR), 2.77; 95% CI, 1.40-5.46]. Furthermore, maternal syphilis was associated with IP/PP HIV MTCT (ARR, 2.74; 95% CI, 1.58-4.74), after adjusting for recent fever, breast infection, LBW and maternal log10 HIV-1 viral load. Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.
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                Author and article information

                Journal
                9805554
                21009
                Sex Transm Infect
                Sex Transm Infect
                Sexually transmitted infections
                1368-4973
                1472-3263
                16 September 2019
                26 July 2017
                December 2017
                21 September 2019
                : 93
                : Suppl 4
                : S3-S15
                Affiliations
                [1 ]London Centre for Nanotechnology, University College London, London, UK
                [2 ]Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
                [3 ]Division of STD Prevention, Center for Disease Control and Prevention, Atlanta, Georgia, USA
                [4 ]Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland
                Author notes
                Correspondence to: Dr Melanie M Taylor, Department of Reproductive Health and Research, World Health Organization, 20 Avenue Appia, Geneva 1211, Switzerland; mtaylor@ 123456who.int

                Contributors HDG, MMT and TW planned the systematic review. HDG and MMT designed the methodology, collected and analysed the data and wrote the manuscript. HDG, MLK, IT, RP, TW and MMT reviewed and edited the manuscript.

                Article
                HHSPA1050480
                10.1136/sextrans-2016-053069
                6754342
                28747410
                4137214e-0300-4b5d-9a55-8ced5b4074bc

                This is an open access article distributed under the terms of the Creative Commons Attribution IGO License ( https://creativecommons.org/licenses/by/3.0/igo), which permits use, distribution, and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.

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