Browsing by Author "Theron, Gerhard"

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    Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission
    (PLOS, 2018-01-05) Adachi, Kristina; Xu, Jiahong; Yeganeh, Nava; Camarca, Margaret; Morgado, Mariza G.; Watts, D. Heather; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Moye, Jack; Klausner, Jeffrey D.; Bristow, Claire C.; Dickover, Ruth; Mirochnick, Mark; Nielsen, Karin
    Background: Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology: Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results: A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1–3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5–7.7). Individually, maternal CMV (aOR 4.4 1.5–13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2–7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion: HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.
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    Effects of pregnancy and isoniazid preventive therapy on mycobacterium tuberculosis interferon gamma response assays in women with HIV
    (Oxford University Press, 2020-07) Weinberg, Adriana; Aaron, Lisa; Montepiedra, Grace; Sterling, Timothy R.; Browning, Renee; Mmbaga, Blandina; Vhembo, Tichaona; Naik, Shilpa; Kabugho, Enid; Masheto, Gaerolwe; Pahwa, Savita; Mathad, Jyoti S.; LaCourse, Sylvia M.; McCarthy, Katie; Bradford, Sarah; Theron, Gerhard; Costello, Diane; Zimmer, Bonnie; Pierre, Marie F.; Gausi, Kamunkhwala; Denti, Paolo; Haas, David W.; Gupta, Amita
    Background Pregnancy is accompanied by immune suppression. We hypothesized that Mycobacterium tuberculosis-specific inflammatory responses used to identify latent tuberculosis infection (LTBI) lose positivity during pregnancy. We also hypothesized that isoniazid preventive therapy (IPT) may revert LTBI diagnoses because of its sterilizing activity. Methods 944 women with human immunodeficiency virus infection (HIV) participating in a randomized, double-blind, placebo-controlled study comparing 28 weeks of IPT antepartum versus postpartum, were tested by QuantiFERON-gold-in-tube (QGIT) antepartum and by QGIT and tuberculin skin test (TST) at delivery and postpartum. Serial QGIT positivity was assessed by logistic regression using generalized estimating equations. Results From entry to delivery, 68 (24%) of 284 QGIT-positive women reverted to QGIT-negative or indeterminate. Of these, 42 (62%) recovered QGIT positivity postpartum. The loss of QGIT positivity during pregnancy was explained by decreased interferon gamma (IFNγ) production in response to TB antigen and/or mitogen. At delivery, LTBI was identified by QGIT in 205 women and by TST in 113 women. Corresponding numbers postpartum were 229 and 122 women. QGIT and TST kappa agreement coefficients were 0.4 and 0.5, respectively. Among QGIT-positive women antepartum or at delivery, 34 (12%) reverted to QGIT-negative after IPT. There were no differences between women who initiated IPT antepartum or postpartum. Conclusions Decreased IFNγ responses in pregnancy reduced QGIT positivity, suggesting that this test cannot reliably rule out LTBI during pregnancy. TST was less affected by pregnancy, but had lower positivity compared to QGIT at all time points. IPT was associated with loss of QGIT positivity, the potential clinical consequences of which need to be investigated.
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    HIV transmission from mother to child : HAART compared with dual therapy
    (Health and Medical Publishing Group (HMPG), 2009-10) Theron, Gerhard; Nellensteijn, Myrthe; Theron, Anneke; Louw, Jeanne
    There are increasing calls for the use of highly active antiretroviral therapy (HAART) for the prevention of perinatal mother-to-child transmission (PMTCT) of HIV.1 This approach does not recognise the weaknesses in health systems to implement complex treatment protocols. In addition, the safety of HAART during pregnancy is uncertain and the consequences of stopping HAART if not required outside pregnancy are unknown. If the same PMTCT of HIV could be attained with a simple regimen with proven safety and known adverse drug effects, this would be a better option in most under-resourced countries.2 The superiority of HAART compared with dual therapy according to World Health Organization (WHO) recommendations for immune-competent women to reduce PMTCT has not been proven.3 We aimed to determine whether there is a difference in perinatal HIV transmission on HAART therapy compared with the national dual-therapy regimen. In addition, the relation between CD4 counts and transmission in the dual-therapy group was investigated.
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    Individual and composite adverse pregnancy outcomes in a randomized trial on isoniazid preventative therapy among women living with human immunodeficiency virus
    (Oxford University Press, 2021-06-01) Theron, Gerhard; Montepiedra, Grace; Aaron, Lisa; McCarthy, Katie; Chakhtoura, Nahida; Jean-Philippe, Patrick; Zimmer, Bonnie; Loftis, Amy James; Chipato, Tsungai; Nematadzira, Teacler; Nyati, Mandisa; Onyango-Makumbi, Carolyne; Masheto, Gaerolwe; Ngocho, James; Tongprasert, Fuanglada; Patil, Sandesh; Lespinasse, Dominique; Weinberg, Adriana; Gupta, Amita
    Background: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. Methods: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. Results: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). Conclusions: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.
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    Introducing a mobile-connected umbilical doppler device (UmbiFlow™) into a primary care maternity setting : does this reduce unnecessary referrals to specialised care? results of a pilot study in Kraaifontein, South Africa
    (Public Library of Science, 2015-11) Mufenda, Josef; Gebhardt, Stefan; Van Rooyen, Rita; Theron, Gerhard
    Objectives: UmbiFlow™ is a mobile-connected Doppler device that utilises a continuous waveform to measure resistance in the umbilical artery. The main aim of this pilot study was to determine whether the use of UmbiFlow™ for umbilical artery Doppler in patients with a suspected decreased symphysis fundal (SF) growth could safely lead to a decreased number of patients requiring referral to a more specialised level of care. A secondary aim of the study was to evaluate the effectiveness of UmbiFlow™ Doppler as a screening tool for concealed placental insufficiency in late bookers by using a single screening cut-off value that will be abnormal for any gestation >28 weeks. Methods: The cohort comprised two groups of patients: The first group included all follow-up patients with suspected intra-uterine growth restriction (a decreased symphysis-fundus measurement based on serial assessment) who underwent on-site UmbiFlow™Doppler testing performed by the midwife directly after the clinical examination. The second group included late bookers, where gestation was uncertain; but estimated >28 weeks based on clinical grounds. This group was comprised of unselected patients who report to antenatal care late for the first time and received an UmbiFlow™Doppler test for concealed placental insufficiency. Results: UmbiFlow™Doppler could reduce the number of false referrals to hospital by 55%. A single UmbiFlow™Doppler test in late bookers appeared to identify a group of women at moderate risk of lower birth weight babies.
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    Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women
    (Massachusetts Medical Society, 2019-10-03) Gupta, Amita; Montepiedra, Grace; Aaron, Lisa; Theron, Gerhard; McCarthy, Katie; Bradford, Sarah; Chipato, Tsungai; Vhembo, Tichaona; Stranix-Chibanda, Lynda; Onyango-Makumbi, Carolyne; Masheto, Gaerolwe R.; Mmbaga, Blandina T.; Aurpibul, Linda; Bhosale, Ramesh; Mave, Vidya; Rouzier, Vanessa; Hesseling, Anneke; Shin, Katherine; Zimmer, Bonnie; Costello, Diane; Sterling, Timothy R.; Chakhtoura, Nahida; Jean-Philippe, Patrick; Weinberg, Adriana
    BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], −4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, −0.39; 95% CI, −1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, −0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038. opens in new tab.)
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    Major obstetric haemorrhage in Metro East, Cape Town, South Africa : a population-based cohort study using the maternal near-miss approach
    (BMC (part of Springer Nature), 2020-01-06) Heitkamp, Anke; Aronson, Simcha Lot; Van Den Akker, Thomas; Vollmer, Linda; Gebhardt, Stefan; Van Roosmalen, Jos; De Vries, Johanna I.; Theron, Gerhard
    Background: Major obstetric haemorrhage is a leading cause of maternal mortality and accounts for one-third of maternal deaths in of Africa. This study aimed to assess the population-based incidence, causes, management and outcomes of major obstetric haemorrhage and risk factors associated with poor maternal outcome. Methods: Women with major obstetric haemorrhage who met the WHO maternal near-miss criteria or died in the Metro East region, Cape Town, South Africa, were evaluated from November 2014–November 2015. Major obstetric haemorrhage was defined as haemorrhage in pregnancies of at least 20 weeks’ gestation or occurring up to 42 days after birth, and leading to hysterectomy, hypovolaemic shock or blood transfusion of ≥5 units of Packed Red Blood Cells. A logistic regression model was used to analyse associations with poor outcome, defined as major obstetric haemorrhage leading to massive transfusion of ≥8 units of packed red blood cells, hysterectomy or death. Results: The incidence of major obstetric haemorrhage was 3/1000 births, and the incidence of massive transfusion was 4/10.000 births in the Metro East region (32.862 births occurred during the studied time period). Leading causes of haemorrhage were placental abruption 45/119 (37.8%), complications of caesarean section 29/119 (24.4%) and uterine atony 13/119 (10.9%). Therapeutic oxytocin was administered in 98/119 (82.4%) women and hysterectomy performed in 33/119 (27.7%). The median numbers of packed red blood cells and units of Fresh Frozen Plasma transfused were 6 (interquartile range 4–7) and 3 (interquartile range 2–4), ratio 1.7:1. Caesarean section was independently associated with poor maternal outcome: adjusted OR 4.01 [95% CI 1.58, 10.14]. Conclusions: Assessment of major obstetric haemorrhage using the Maternal Near Miss approach revealed that placental abruption and complications of caesarean section were the major causes of major obstetric haemorrhage. Caesarean section was associated with poor outcome.
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    Pandemic flu (H1N1) 2009 and pregnancy
    (Health and Medical Publishing Group (HMPG), 2010-04) Andersson, Monique I.; Van Zyl, Gert; Preiser, Wolfgang; Langenegger, Eduard; Theron, Gerhard
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    Pregnancy outcomes of women conceiving on antiretroviral therapy (ART) compared to those commenced on ART during pregnancy
    (Oxford University Press, 2021-07) Theron, Gerhard; Brummel, Sean; Fairlie, Lee; Pinilla, Mauricio; McCarthy, Katie; Owor, Maxensia; Chinula, Lameck; Makanani, Bonus; Violari, Avy; Moodley, Dhayendre; Chakhtoura, Nahida; Browning, Renee; Hoffman, Risa; Fowler, Mary Glenn
    Background: Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods: The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. Results: Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500 g) for women who conceived while on ART (relative risk, 2.65 [95% confidence interval {CI}, 1.20-5.81]), and also a higher risk of spontaneous abortion, stillbirth, or neonatal death (hazard ratio, 1.40 [95% CI, .99-1.98]) compared to women who restarted ART after they were found to be pregnant during trial follow-up. Conclusions: We found an increased risk for adverse pregnancy outcomes in women conceiving on ART, emphasizing the need for improved obstetric and neonatal care for this group. Clinical trials registration: NCT01061151.
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    Severe acute respiratory infection with influenza A (H1N1) during pregnancy
    (Health and Medical Publishing Group (HMPG), 2009-10) Langenegger, Eduard; Coetzee, Andre; Jacobs, Samier; Le Roux, Alrisah; Theron, Gerhard
    ABSTRACT FROM JOURNAL: Pregnant women are at high risk of severe acute respiratory infection if infected with the influenza A (H1N1) virus. On 14 August 2009 the first complicated H1N1 obstetric patient was admitted to the obstetric critical care unit (OCCU) at Tygerberg Hospital with respiratory distress. The clinical picture was that of bronchopneumonia, and she tested positive for H1N1. Subsequent pregnant patients admitted to the OCCU with respiratory compromise or flu symptoms were screened for the virus. Eleven days later 13 cases were confirmed. Five patients had acute lung injury and required ventilation and inotropic support. Three of the patients with acute lung injury subsequently died. Three patients required continuous positive airway pressure (CPAP) support only, with no inotropics needed. The remaining 5 patients presented early, received oseltamivir within 48 hours and did not require critical care admission. All the patients admitted to the OCCU and the medical intensive care unit (ICU) initially presented with flu symptoms, respiratory distress and changes on the chest radiograph indicating an active diffuse pulmonary parenchymal process. Six patients underwent uncomplicated caesarean sections for fetal distress after they were stabilised. Maternal and neonatal outcomes varied. The key factor appears to be early clinical diagnosis and oseltamivir within 48 hours of the onset of symptoms. The demographic data and maternal and fetal outcomes are set out in Table I.
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    Total perinatally related losses at Tygerberg hospital : a comparison between 1986, 1993 and 2006
    (Health and Medical Publishing Group (HMPG), 2010) Talip, Quonita; Theron, Gerhard; Steyn, Wilhelm; Hall, David R.
    Objective. To determine the leading causes of perinatal deaths and to evaluate any changes, with the inclusion of placental histology. Method. At perinatal mortality meetings, primary and final causes of death were assigned for the period 1 July 2006 - 30 June 2007. All singleton babies born to women residing in the metropolitan area serviced by Tygerberg Hospital were included in the prospective descriptive study. Results. The total number of singleton births was 10 396. The total of perinatally related losses (TPRL) rate was 26.2 per 1 000 births. The leading primary obstetric causes of death were: infections (47 - 17.3%), spontaneous preterm labour (PTL) (41 - 15.1%), antepartum haemorrhage (APH) (40 - 14.7%), intra-uterine growth restriction (IUGR) (40 - 14.7%), fetal abnormality (31 - 11.4%), hypertensive disorders (25 - 9.2%), unexplained intra-uterine deaths (IUD) (20 - 7.4%), intrapartum hypoxia (12 - 4.4%) and maternal disease (9 - 3.3%). A total of 162 placentas were sent for histology; 58 reports changed the primary cause of death. Conclusion. The TPRL rate for singleton pregnancies was 26.2 per 1 000 births for the study period. The TPRL rates in 1986 and 1993 were 36.7 and 30.5 per 1 000 deliveries. Infection is now the leading primary cause of death, followed by spontaneous PTL, APH and IUGR. During the previous two study periods, APH was the leading primary cause of death, followed by spontaneous PTL. Unexplained IUDs ranked third in 1986, fourth in 1993 and seventh in this study because of the availability of placental histology. Placental histology reports changed 21.3% of the primary causes of death.
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    Using a composite maternal-infant outcome measure in tuberculosis prevention studies among pregnant women
    (Oxford University Press, 2021-08-02) Montepiedra, Grace; Kim, Soyeon; Weinberg, Adriana; Theron, Gerhard; Sterling, Timothy R.; LaCourse, Sylvia M.; Bradford, Sarah; Chakhtoura, Nahida; Jean-Philippe, Patrick; Evans, Scott; Gupta, Amita
    Background: Tuberculosis (TB-)-preventive therapy (TPT) among pregnant women reduces risk of TB in mothers and infants, but timing of initiation should consider potential adverse effects. We propose an analytical approach to evaluate the risk-benefit of interventions. Methods: A novel outcome measure that prioritizes maternal and infant events was developed with a 2-stage Delphi survey, where a panel of stakeholders assigned scores from 0 (best) to 100 (worst) based on perceived desirability. Using data from TB APPRISE, a trial among pregnant women living with human immunodeficiency virus (WLWH) that randomized the timing of initiation of isoniazid, antepartum versus postpartum, was evaluated. Results: The composite outcome scoring/ranking system categorized mother-infant paired outcomes into 8 groups assigned identical median scores by stakeholders. Maternal/infant TB and nonsevere adverse pregnancy outcomes were assigned similar scores. Mean (SD) composite outcome scores were 43.7 (33.0) and 41.2 (33.7) in the antepartum and postpartum TPT initiation arms, respectively. However, a modifying effect of baseline antiretroviral regimen was detected (P = .049). When women received nevirapine, composite scores were higher (worse outcomes) in the antepartum versus postpartum arms (adjusted difference, 14.3; 95% confidence interval [CI], 2.4-26.2; P = .02), whereas when women received efavirenz there was no difference by timing of TPT (adjusted difference, .62; 95% CI, -3.2-6.2; P = .53). Conclusions: For TPT, when used by otherwise healthy persons, preventing adverse events is paramount from the perspective of stakeholders. Among pregnant WLWH in high-TB-burden regions, it is important to consider the antepartum antiretroviral regimen taken when deciding when to initiate TPT. Clinical Trials Registration. NCT01494038 (IMPAACT P1078).