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      Improving early identification of HIV-infected neonates with birth PCR testing in a large urban hospital in Johannesburg, South Africa: successes and challenges

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          Abstract

          Introduction: Timely diagnosis is necessary to avert early death in HIV-infected neonates. Birth PCR testing may improve early identification and facilitate access to care. We implemented a birth HIV diagnosis programme in Johannesburg, South Africa and present successes and challenges of the first two and a half years of operation.

          Methods: Between June 2014 and December 2016, we sought to identify all HIV-exposed births and offer newborn HIV PCR testing before discharge after delivery. The programme identified newly delivered women who had tested positive during pregnancy and provided post-partum HIV antibody testing for women without recent negative results. HIV-positive women were required to consent for neonatal birth testing and asked to return a week later to obtain their results. Neonatal venous blood was sampled and tested at the national laboratory using Roche COBAS® TaqMan® HIV-1 Qualitative Test (Version 2.0). Non-negative results triggered active follow-up for confirmatory testing and appropriate treatment.

          Results: Of 30,591 women with live births, 6864 (22.4%) were known to be HIV positive and an additional 221 women (1.4% of those tested) were identified during maternal postnatal testing. Of 7085 HIV-positive women, 6372 (89.9%) were interviewed and agreed to data collection, 6358 (99.8%) consented to birth testing for 6467 neonates and a blood sample was collected for 6377 (98.6%). If tested, 6210 (97.4%) tested negative, 91 (1.4%) positive, 57 (0.9%) revealed errors and 19 (0.3%) were indeterminate . Seven of the 19 neonates with indeterminate results and one with initial error result were found to be infected on subsequent testing yielding an intrauterine transmission rate of 1.6% (95% CI: 1.3–1.9). Sixteen (16%) of 99 infected infants were born to women ( n = 221) identified during postnatal testing. With active outreach, 95/99 (96%) infected infants were initiated on antiretroviral therapy. Of 6261 neonates with negative results, 3251 (52%) returned to receive their test results.

          Conclusion: Our programme successfully achieved high coverage and uptake of birth PCR testing and was able, with active tracking, to start almost all identified HIV-infected neonates on antiretroviral therapy. Implementation required additional staff for counselling, quality control and outreach. Return for negative results was low and neonates with indeterminate results required multiple repeat tests.

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          Most cited references 12

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          New Ballard Score, expanded to include extremely premature infants.

          The Ballard Maturational Score was refined and expanded to achieve greater accuracy and to include extremely premature neonates. To test validity, accuracy, interrater reliability, and optimal postnatal age at examination, the resulting New Ballard Score (NBS) was assessed for 578 newly born infants and the results were analyzed. Gestational ages ranged from 20 to 44 weeks and postnatal ages at examination ranged from birth to 96 hours. In 530 infants, gestational age by last menstrual period was confirmed by agreement within 2 weeks with gestational age by prenatal ultrasonography (C-GLMP). For these infants, correlation between gestational age by NBS and C-GLMP was 0.97. Mean differences between gestational age by NBS and C-GLMP were 0.32 +/- 1.58 weeks and 0.15 +/- 1.46 weeks among the extremely premature infants (less than 26 weeks) and among the total population, respectively. Correlations between the individual criteria and C-GLMP ranged from 0.72 to 0.82. Interrater reliability of NBS, as determined by correlation between raters who rated the same subgroup of infants, ws 0.95. For infants less than 26 weeks of gestational age, the greatest validity (97% within 2 weeks of C-GLMP) was seen when the examination was performed before 12 hours of postnatal age. For infants at least 26 weeks of gestational age, percentages of agreement with C-GLMP remained constant, averaging 92% for all postnatal age categories up to 96 hours. The NBS is a valid and accurate gestational assessment tool for extremely premature infants and remains valid for the entire newborn infant population.
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            Emergence of a peak in early infant mortality due to HIV/AIDS in South Africa.

            South Africa has among the highest levels of HIV prevalence in the world. Our objectives are to describe the distribution of South African infant and child mortality by age at fine resolution, to identify any trends over recent time and to examine these trends for HIV-associated and non HIV-associated causes of mortality. A retrospective review of vital registration data was conducted. All registered postneonatal deaths under 1 year of age in South Africa for the period 1997-2002 were analysed by age in months using a generalized linear model with a log link and Poisson family. Postneonatal mortality increased each year over the period 1997-2002. A peak in HIV-related deaths was observed, centred at 2-3 months of age, rising monotonically over time. We interpret the peak in mortality at 2-3 months as an indicator for paediatric AIDS in a South African population with high HIV prevalence and where other causes of death are not sufficiently high to mask HIV effects. Intrauterine and intrapartum infection may contribute to this peak. It is potentially a useful surveillance tool, not requiring an exact cause of death. The findings also illustrate the need for early treatment of mother and child in settings with very high HIV prevalence.
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              Surveillance of mother-to-child transmission prevention programmes at immunization clinics: the case for universal screening.

              Surveillance programmes for prevention of mother-to-child transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections averted, often because of poor postnatal follow-up. Additionally, infected infants are often not identified early and only gain access to comprehensive HIV care and treatment late in their disease. Anonymous, unlinked, HIV prevalence testing was conducted on dried blood spot (DBS) samples from all infants attending 6 week immunization clinics at seven primary health care clinics offering PMTCT. Samples were tested for HIV antibodies (indicating maternal HIV infection) and those determined to be from HIV-exposed infants were tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates were determined using birth histories. Samples were collected from 2489 infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95% confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5% of all infants at this age were infected. Amongst mothers who reported that they had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who reported being HIV uninfected but whose infants had HIV antibodies, VTR was 30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births in 1990-1994 to 92/1000 in 2000-2004. Anonymous HIV prevalence screening of all infants at immunization clinics is feasible to monitor the impact of PMTCT programmes on peripartum infection; linked screening could identify infected children early for referral into care and treatment programmes.
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                Author and article information

                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                ZIAS
                zias20
                Journal of the International AIDS Society
                Taylor & Francis
                1758-2652
                2017
                10 April 2017
                : 20
                : 1
                Affiliations
                [ a ] Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand , South Africa
                [ b ] Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University , New York, NY, USA
                [ c ] Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service , Johannesburg, South Africa
                [ d ] Centre for HIV and STI, National Institute for Communicable Diseases , Johannesburg, South Africa
                Author notes
                [ § ]Corresponding author: Karl-Günter Technau, Department of Paediatrics, Rahima Moosa Mother and Child Hospital , Cnr Oudtshoorn and Fuel Rd, Coronationville 2000, South Africa. ( karl-gunter.technau@ 123456wits.ac.za )
                Article
                1309863
                10.7448/IAS.20.01/21436
                5515050
                28406596
                © 2017 Technau K-G et al; licensee International AIDS Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 4, References: 25, Pages: 9
                Product
                Funding
                We gratefully acknowledge the National and Gauteng Provincial Department of Health for their support and funding of HIV tests. The study 505AQ3 was supported in part by the National Institutes of Health U01 HD080441. Funders played no role in study design.
                Categories
                Article
                Research

                Infectious disease & Microbiology

                hiv, diagnosis, neonate, polymerase chain reaction, birth, in-utero

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