Congenital Rubella Syndrome Surveillance in South Africa Using a Sentinel Site Approach: A Cross-sectional Study.

BACKGROUND: Congenital rubella syndrome (CRS) includes disorders associated with intrauterine rubella infection. Incidence of CRS is higher in countries with no rubella-containing vaccines (RCV) in their immunization schedules. In the World Health Organization African region, RCVs are being introduced as part of the 2012-2020 global measles and rubella strategic plan. This study aimed to describe the epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in the immunization schedule. METHODS: This was a descriptive study with 28 sentinel sites reporting laboratory-confirmed CRS cases in all 9 provinces of South Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from medical records, and in the prospective phase (2015 to 2017) clinicians at study sites reported CRS cases monthly. RESULTS: There were 42 confirmed CRS cases in the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most frequently reported birth defects were congenital heart disease and cataracts. The median age of mothers of CRS cases was 21 years in the retrospective phase (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38 years). CONCLUSION: Baseline data on laboratory-confirmed CRS will enable planning and monitoring of RCV implementation in the South African Expanded Programme on Immunization program. Ninety-eight percent of mothers of infants with CRS were young women 14-30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV.

HIV-1 disease progression in immune-competent HIV-1-infected and breastfeeding mothers participating in the ANRS 12174 clinical trial in Burkina Faso, South Africa, Uganda and Zambia: a cohort study.

OBJECTIVE: We have assessed HIV-1 disease progression among HIV-1-positive mothers in relation to duration of any or exclusive breast feeding in the context of ANRS 12174 trial. METHODS: The analysis was completed on 203, 212, 272 and 529 HIV-1-positive and lactating mothers with CD4 count >350 cells/µL from Burkina Faso, South Africa, Uganda and Zambia, respectively. The trial compared lamivudine and lopinavir/ritonavir as a peri-exposure prophylaxis during a 50-week follow-up time. A multiple logistic regression model was run with the mothers' weight, CD4 count and HIV-1 viral load as separate dependent variables, then combined into a dependent composite endpoint called HIV-1 disease progression where HIV-1 viral load was replaced by the HIV-1 clinical stage. Exclusive or predominant breast feeding (EPBF) and any breastfeeding duration were the key explanatory variables. RESULTS: In the adjusted model, the associations between EPBF duration and weight change, CD4 cell count and the HIV-1 viral load were consistently insignificant. The CD4 cell count was associated with a significantly higher mothers' body mass index (BMI; a mean increase of 4.9 (95% CI 2.1 to 7.7) CD4 cells/µL per each additional kilogram per square metre of BMI) and haemoglobin concentration (19.4 (95% CI 11.4 to 27.4) CD4 cells/µL per each additional gram per decilitre of haemoglobin concentration). There was no significant association between EPBF duration and HIV-1 disease progression. A higher education level was a factor associated with a slower HIV-1 disease progression. CONCLUSION: Breast feeding was not a risk factor for a faster progression of HIV-1 disease in mothers of this cohort with a baseline CD4 cell count >350 cells/µL. TRIAL REGISTRATION NUMBER: NCT0064026; Post-results.

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding.

The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.).

Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected Children Unable to Adhere to Triple Therapy.

BACKGROUND: HIV-infected children in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. METHODS: A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200cells/µl, n=64; Group 2: ≤200cells/µl, n=7). Study endpoints were defined as a decline of absolute CD4 by ≥25% or to ≤200 cells/µl or World Health Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of second- or third-line therapy (real-world outcomes). RESULTS: Eligible LM events were identified among 71 children (56.4% male; median age at LM initiation 9.6 years). 71.8% (n = 51) had a drop in CD4 count of ≥25%, 15.6% (n = 10) of those whose CD4 counts had been >200 cells/µl dropped to ≤200 cells/µl and 8.1% (n = 6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did not differ significantly between groups. No deaths were recorded. Children commencing LM with CD4 counts ≤200cells/µl had a shorter mean "real-world" duration of LM before switching to second/third line therapy (11.38 months vs. 26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage (5.29 vs. 9.2 months, P = 0.023). CONCLUSIONS: LM offers a potential alternative approach to antiretroviral therapy management in young patients pending availability and/or willingness to adhere to second- or third-line therapies but is associated with substantial immunologic decline. This strategy should be avoided in patients with CD4 ≤200 cells/µl.

Breastfeeding patterns and its determinants among mothers living with Human Immuno-deficiency Virus -1 in four African countries participating in the ANRS 12174 trial.

BACKGROUND: HIV-1 transmission rates have been reduced over the last decade, an estimated 2 million new infections per year arise, including 220,000 paediatric cases. The main post-natal HIV exposure is through breastfeeding, where both its duration and modality (exclusive or not) are associated with postnatal transmission. The ANRS 12174 trial compared HIV-1 postnatal transmission of 2 prophylaxis drugs for infants during lactation (lamivudine and lopinavir-ritonavir). Our objective has been to examine the feeding practices and the determinants of exclusive/ predominant (EPBF) or any breastfeeding among the participants of this trial in Burkina Faso, South Africa, Uganda and Zambia. METHODS: Mothers infected with HIV-1 and their uninfected offspring were followed from day 7 after birth for 50 weeks, keeping monthly records of their feeding patterns. Feeding was classified into 3 categories: 1) exclusive breastfeeding during the first six months, only breast-milk being given to infant for 6 months, 2) predominant breastfeeding, breast-milk with liquid-based items being given, and 3) mixed feeding, other non-breast milk or solid food being given in addition to breast milk with or without liquid-based items. The categories were merged into 2 groups: EPBF applying to infants aged <6 months and mixed feeding applying to infants of any age. The feeding patterns have been given as Kaplan-Meier curves. A flexible parametric multiple regression model was used to identify the determinants of the mothers' feeding behaviour. RESULTS: A total of 1,225 mother-infant pairs provided feeding data from Burkina Faso (N = 204), South Africa (N = 213), Uganda (N = 274) and Zambia (N = 534) between November 2009 and March 2013. The mean maternal age was 27.4 years and the mean BMI was 24.5. 57.7 and 93.9% of mothers initiated breastfeeding within the first hour and first day, respectively. Overall, the median durations of any form of breastfeeding and EPBF were 40.6, and 20.9 weeks, respectively. Babies randomized to the lopinavir/ritonavir group in South Africa tended to do less EPBF than those in the lamivudine group. Overall the group of mothers aged between 25 and 30 years, those married, employed or multiparous tended to stop early EPBF. Mothers living in Uganda or Zambia, those aged between 25 -30 years, better educated (at least secondary school level), employed or having undergone C-section stopped any breastfeeding early. CONCLUSIONS: There is a need to improve breastfeeding and complementary feeding practices of children, particularly those exposed to HIV and anti-retrovirals, taking into account context and socio-demographic factors. TRIAL REGISTRATION: Clinical trial registration: NCT00640263.

Lamivudine monotherapy as a safe option for HIV-infected paediatric clients with adherence challenges: new evidence from a large South African cohort.

INTRODUCTION: HIV-infected children in resource-poor settings comprise a unique population who require antiretroviral therapy (ART) in careful consideration of social and structural barriers to compliance. Given these aggregate challenges and emerging research into "holding" treatment options, we investigated the efficacy of lamivudine monotherapy (LM) as an alternative to more complex second and third line therapies. METHODS: A retrospective review of all eligible LM events (=6 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200 cells/L, n=64; Group 2:=200cells/L, n=10). Study endpoints were defined as a decline of absolute CD4=200 cells/L (Group 1), WHO stage 3 or 4 event (Groups 1& 2), or initiation of second or third line (Groups 1 & 2). RESULTS: Seventy-four eligible LM events were identified among 71 HIV-positive children (58% male; median age at LM 9.7 years and median LM duration 11.5 months). CD4 decreases and measured WHO stage 3 or 4 events did not yield overall significance between groups (Table 1). No deaths were recorded. CONCLUSIONS: LM offers a promising alternative approach to ART management in young patients with an absolute CD4 >200 cells/L pending availability and/or willingness to adhere to second or third line therapies. In more immunocompromised children, LM may be considered as a last option if either the child or caretaker has concerns about second or third line management, or has defaulted repeatedly.

Group work with female survivors of childhood sexual abuse: evidence of poorer outcomes among those with eating disorders.

OBJECTIVE: This study explored levels of depression and self-esteem after childhood sexual abuse (CSA) group treatment for survivors with and without histories of eating disorders (ED). METHODS: Fifty adult female survivors completed a 15-week CSA group treatment program and were assessed at intake, pre-group treatment, discharge, and six months follow-up using the Beck Depression Inventory, the Generalized Contentment Scale and the Index of Self-Esteem. They were also asked to report on their CSA histories and comorbid psychiatric issues including histories of ED. RESULTS: Survivors with reported histories of anorexia nervosa or bulimia nervosa were significantly more depressed (minimum p<.05) and tended to have significantly less self-esteem (minimum p<.10) at discharge and six-month follow-up than those without ED. The size of these effects suggested their potential clinical significance as well. Seven to nine of every ten clients with histories of ED were more depressed and had lower self-esteem than the typical client without ED at discharge and at six-month follow-up. CONCLUSION: The findings suggest that CSA treatment programs should assess survivors for ED as they might benefit from a more specialized focus on their emotional responses to the abuse.

Insecure attachment as a predictor of outcome following inpatient trauma treatment for women survivors of childhood abuse.

The role of insecure attachment as a predictor of outcome was investigated in 134 women who reported histories of child abuse and completed an inpatient program for treatment of traumatic stress. Multiple linear regressions were used to predict the change scores on four outcome measures at discharge and 6-month follow-up. Higher levels of feared loss of the attachment figure independent of demographics, symptomatic severity, and trauma exposure consistently predicted poorer outcome at both post-tests. Interventions that focus on internal models of attachment and current attachment relationships may improve outcome in women reporting severe abuse in childhood.

What works for survivors of childhood abuse: learning from participants in an inpatient treatment program.

Thirty adults were interviewed about their experiences in a 6-week program for recovery from posttraumatic stress. The most valued aspects were their relationships with staff and the staff's expertise in treating the long-term effects of abuse. They valued the structured group treatment that allowed them to process emotions with the goal of healing. A few were upset by process groups, whereas others had difficulty with the sudden loss of support at discharge from the program.

Therapeutic boundary issues in working with childhood sexual-abuse survivors.

The article describes a study of therapists involved in treating survivors of childhood sexual abuse. The authors focus on what induces participants to change their usual therapeutic boundaries. Through qualitative research utilizing extensive interviews, written questionnaires, and a focus-group discussion, the authors gathered information from therapists related to situations that influence them to change their own boundaries. Emergent themes are discussed and the information is integrated with the authors' experience of supervision and psychotherapy. Concern for client safety is the commonly recurrent issue that pushes therapists to change their boundaries. Other intense feelings, such as resentment of the client, worry about the client's feelings, a wish to connect and imbue hope are also strong influences. Self-disclosure boundaries of the therapist are challenged by the wish to balance power within the relationship. Supervision provides an opportunity to examine what influences therapists to make subtle boundary shifts before they become harmful boundary crossings.