How to use autoantibodies in suspected paediatric rheumatic disease.

Autoantibodies can be an important indicator of paediatric rheumatic disease and useful in establishing a diagnosis. However, autoantibodies may be requested in cases where the patient does not have clinical features strongly suggestive of a rheumatic disease. This can lead to further unnecessary investigations, specialist referral and undue anxiety for the family. The aim of this article is to provide guidance for when it is appropriate to request autoantibodies, which ones to perform and how to interpret the results.

Breastfeeding, HIV exposure, childhood obesity, and prehypertension: A South African cohort study.

BACKGROUND: Evidence on the association between breastfeeding and later childhood obesity and blood pressure (BP) is inconsistent, especially in HIV-prevalent areas where, until recently, HIV-infected women were discouraged from breastfeeding, but obesity is increasingly prevalent. METHODS AND FINDINGS: The Siyakhula cohort (2012-2014), a population-based prospective cohort study, collected data over 3 visits on HIV-negative children ages 7 to 11 years in rural South Africa. We used weight (body mass index [BMI]), fat, and BP as outcome variables and incorporated early life (including mother's age at delivery and HIV status) and current life factors (including maternal education and current BMI). Our primary exposure was breastfeeding duration. We dichotomized 3 outcome measures using pre-established thresholds for clinical interpretability: (1) overfat: ≥85th percentile of body fat; (2) overweight: >1 SD BMI z score; and (3) prehypertension: ≥90th percentile for systolic BP (SBP) or diastolic BP (DBP). We modelled each outcome using multivariable logistic regression, including stopping breastfeeding, then early life, and finally current life factors. Of 1,536 children (mean age = 9.3 years; 872 girls; 664 boys), 7% were overfat, 13.2% overweight, and 9.1% prehypertensive. Over half (60%) of the mothers reported continued breastfeeding for 12+ months. In multivariable analyses, continued breastfeeding between 6 and 11 months was associated with approximately halved odds of both being overfat (adjusted odds ratio [aOR] = 0.43, 95% confidence interval [CI] 0.21-0.91, P = 0.027) and overweight (aOR = 0.46, CI 0.26-0.82, P = 0.0083), but the association with prehypertension did not reach statistical significance (aOR = 0.72, CI 0.38-1.37, P = 0.32). Children with a mother who was currently obese were 5 times more likely (aOR = 5.02, CI 2.47-10.20, P < 0.001) to be overfat and over 4 times more likely to be overweight (aOR = 4.33, CI 2.65-7.09, P < 0.001) than children with normal weight mothers. Differences between HIV-exposed and unexposed children on any of the outcomes were minimal and not significant. The main study limitation was that duration of breastfeeding was based on maternal recall. CONCLUSIONS: To our knowledge, this is the first study examining and quantifying the association between breastfeeding and childhood obesity in an African setting with high HIV prevalence. We observed that breastfeeding was independently associated with reduced childhood obesity for both HIV-exposed and unexposed children, suggesting that promoting optimal nutrition throughout the life course, starting with continued breastfeeding, may be critical to tackling the growing obesity epidemic. In the era of widespread effective antiretroviral treatment for HIV-infected women for life, these data further support the recommendation of breastfeeding for all women.

Fever after meningococcal B immunisation: A case series.

AIM: To document the clinical features and management of infants presenting with fever after their first meningococcal B vaccination and develop guidance for clinicians. METHODS: A prospective case series over 12 months was conducted in a tertiary paediatric hospital. Infants ≤3 months of age with fever who had received their first set of immunisations within the preceding 72 h were included. RESULTS: A total of 92 infants met the inclusion criteria, accounting for 0.78% of the local vaccinated population. The most commonly described associated features were poor feeding, sleepiness and irritability; 66 patients (72%) were admitted to hospital. Median C-reactive protein (CRP) was 12 mg/L, and median white cell count (WCC) was 16 × 109 /L. Fifteen patients (16%) had a lumbar puncture and were commenced on antibiotics. There was one confirmed bacterial infection in an infant who had presented with fever starting 54 h after immunisation. All other microbiology samples were negative. There were no cases of missed serious bacterial infection (SBI) in those patients who were observed or discharged. CONCLUSIONS: The routine investigation of infants presenting with post-immunisation fever is not warranted if the infant appears otherwise well on examination. Where other common associated features are present or there is clinical concern, a period of observation is a prudent course of action. Paracetamol should be given peri-immunisation as per the national guidance. We suggest selective use of investigations, especially inflammatory markers, which are unlikely to discriminate between SBI and post-immunisation response. We advocate extra caution in infants presenting with fever more than 48 h after immunisation.

Prevalence and risk factors for child mental disorders in a population-based cohort of HIV-exposed and unexposed African children aged 7-11 years.

Despite being home to a large population of vulnerable children there is a dearth of population-based evidence on childhood mental disorders in sub-Saharan Africa. Parent and child mental health are rarely measured concurrently, despite potential for confounding with other risk factors, including parental HIV. Using the parent-report Child Behaviour Checklist (CBCL) we assessed children's mental health in a population-based cohort of 1536 HIV-negative children (31% HIV-exposed, 18% HIV-affected, 51% HIV-unexposed) aged 7-11 years. CBCL was scored using CBCL Rating-to-Score software. A binary indicator was determined using the clinical threshold ≥ 65. We modelled mental disorders using logistic regression, including covariates associated with the mother, child, household, and parenting. Structural equation modelling techniques also derived continuous latent variables representing the underlying mental health and parent-relationship constructs. Prevalence of conduct disorders (11.8%) was high, regardless of HIV exposure, while HIV-affected children had increased odds of affective disorders. Maternal depression increased odds of externalising disorders; maternal anxiety was associated with affective and anxiety disorders. Mother-child relationship dysfunction increased odds of all disorders, including: affective [aOR = 5.1 (2.6-9.9)]; oppositional [aOR = 7.9 (4.0-15.5)]; conduct [aOR = 4.3 (2.6-7.2)] disorders. Food insecurity and male gender increased odds of somatic disorders; breastfeeding halved odds of conduct disorders. In the latent model, associations were substantially stronger for the mother-child relationship and externalising disorders (Oppositional 0.464 p < 0.001; Conduct 0.474 p = <0.001). Conduct disorders were high for all children regardless of HIV exposure. The mother-child relationship was strongly related to all child disorders, suggesting potential for concurrent interventions targeting child behaviours and the parent-child or mother-child relationship.

Fifteen-minute consultation: The child with an incidental finding of low IgA.

Low or absent immunoglobulin A (IgA) levels are frequently found in children in whom immunodeficiency is not suspected. IgA deficiency is the most common primary immunodeficiency disorder in the UK affecting approximately 1 in 600 people. Isolated IgA deficiency is often identified coincidentally when investigating a child for conditions such as coeliac disease. The aim of this article is to provide a structured approach to the history, investigation and management of an isolated IgA deficiency.

Subclinical mastitis occurs frequently in association with dramatic changes in inflammatory/anti-inflammatory breast milk components.

BACKGROUND: Subclinical mastitis (SCM) is a frequent, but poorly characterized entity that may influence immune development of breastfed infants. Mechanisms driving the emergence of SCM and changes in immunological content of human milk during SCM remain to be explored. In this study, the breast milk environment was to describe during SCM. METHODS: One hundred and ten samples of mature breast milk were collected from 44 healthy, HIV-negative mothers, included in a large infant feeding intervention cohort (ANRS 1271/Vertical Transmission Study). Immune markers related to inflammatory/anti-inflammatory balances and secreted in response to bacterial exposure were explored in SCM breast milk samples (Na/K ratio > 1) and compared to non-SCM controls. RESULTS: SCM was observed in 23% of women (95% confidence interval (CI): 21-24) and associated with higher levels of inflammatory markers (ß2 microgobulin, PS100A9, TNF-α, IL-6, IL-8, IL-17, and RANTES) and Th1-related cytokines (IL-2R, IL-12p40/70, IFN-α, IFN-γ, CXCL-9, andIP-10). High levels of factors secreted in response to bacteria and lipopolysaccharide (LPS) exposure were observed in SCM breast milk samples (MIP-1α, MIP-1ß, LPS binding protein, α-defensins, and antileukoproteinase 1). CONCLUSION: SCM is associated with important changes in breast milk microenvironment, with a proinflammatory/Th1-cytokine predominant profile. During SCM, cytokine imbalances in breast milk may have a notable influence on mucosal immune system of the infant early in life.

Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis.

This study aimed to systematically review and appraise evidence on the short-term (e.g. morbidity, mortality) and long-term (obesity and non-communicable diseases, NCDs) health consequences of catch-up growth (vs. no catch-up growth) in individuals with a history of low birth weight (LBW).We searched MEDLINE, EMBASE, Global Health, CINAHL plus, Cochrane Library, ProQuest Dissertations and Thesis and reference lists. Study quality was assessed using the risk of bias assessment tool from the Agency for Health Care Research and Quality, and the evidence base was assessed using the GRADE tool. Eight studies in seven cohorts (two from high-income countries, five from low-middle-income countries) met the inclusion criteria for short-term (mean age: 13.4 months) and/or longer-term (mean age: 11.1 years) health outcomes of catch-up growth, which had occurred by 24 or 59 months. Of five studies on short-term health outcomes, three found positive associations between weight catch-up growth and body mass and/or glucose metabolism; one suggested reduced risk of hospitalisation and mortality with catch-up growth. Three studies on longer-term health outcomes found catch-up growth were associated with higher body mass, BMI or cholesterol. GRADE assessment suggested that evidence quantity and quality were low. Catch-up growth following LBW may have benefits for the individual with LBW in the short term, and may have adverse population health impacts in the long-term, but the evidence is limited. Future cohort studies could address the question of the consequences of catch-up growth following LBW more convincingly, with a view to informing future prevention of obesity and NCDs. © 2016 John Wiley & Sons Ltd.

Exclusive Breastfeeding and Cognition, Executive Function, and Behavioural Disorders in Primary School-Aged Children in Rural South Africa: A Cohort Analysis.

BACKGROUND: Exclusive breastfeeding (EBF) is associated with early child health; its longer-term benefits for child development remain inconclusive. We examine the associations between EBF, HIV exposure, and other maternal/child factors and the cognitive and emotional-behavioural development of children aged 7-11 y. METHODS AND FINDINGS: The Vertical Transmission Study (VTS) supported EBF in HIV-positive and HIV-negative women; between 2012 and 2014, HIV-negative VTS children (332 HIV exposed, 574 HIV unexposed) were assessed in terms of cognition (Kaufman Assessment Battery for Children Second Edition [KABC-II]), executive function (Developmental Neuropsychological Assessment Second Edition [NEPSY-II]), and emotional-behavioural functioning (parent-reported Child Behaviour Checklist, [CBCL]). We developed population means by combining the VTS sample with 629 same-aged HIV-negative children from the local demographic platform. For each outcome, we split the VTS sample into scores above or at/below each population mean and modelled each outcome using logistic regression analyses, overall and stratified by child sex. There was no demonstrated effect of EBF on overall cognitive functioning. EBF was associated with fewer conduct disorders overall (adjusted odds ratio [aOR] 0.44 [95% CI 0.3-0.7], p ≤ 0.01), and there was weak evidence of better cognition in boys who had been exclusively breastfed for 2-5 mo versus ≤1 mo (Learning subscale aOR 2.07 [95% CI 1.0-4.3], p = 0.05). Other factors associated with better child cognition were higher maternal cognitive ability (aOR 1.43 [95% CI 1.1-1.9], p = 0.02, Sequential; aOR 1.74 [95% CI 1.3-2.4], p < 0.001, Planning subscales) and crèche attendance (aOR 1.96 [95% CI 1.1-3.5], p = 0.02, Sequential subscale). Factors positively associated with executive function were home stimulation (aOR 1.36 [95% CI 1.0-1.8], p = 0.04, Auditory Attention; aOR 1.35 [95% CI 1.0-1.8], p = 0.05, Response Set) and crèche (aOR 1.74 [95% CI 1.0-3.0], p = 0.05, Animal Sorting). Maternal mental health problems and parenting stress were associated with increased emotional-behavioural problems on the total CBCL (aOR 2.44 [95% CI 1.3-4.6], p = 0.01; aOR 7.04 [95% CI 4.2-11.9], p < 0.001, respectively). Maternal HIV status was not associated with any outcomes in the overall cohort. Limitations include the nonrandomised study design and lack of maternal mental health assessment at the child's birth. CONCLUSIONS: EBF was associated with fewer than average conduct disorders and weakly associated with improved cognitive development in boys. Efforts to improve stimulation at home, reduce maternal stress, and enable crèche attendance are likely to improve executive function and emotional-behavioural development of children.

Impact of adherence to WHO infant feeding recommendations on later risk of obesity and non-communicable diseases: systematic review.

Adherence to WHO infant feeding recommendations has short-term benefits and may also help in the prevention of non-communicable diseases (NCDs). This study reviewed the evidence on whether adherence to all elements of the WHO infant feeding recommendations (comparison group those exclusively breastfed to 6 months, introduced to appropriate complementary feeding from 6 months, with continued breastfeeding to at least 24 months; exposure group characterised by non-adherence to any of the three recommendations) is associated with reduced risk of later obesity or cardiometabolic disease. The population of interest was children not classified as very low weight (weight-for-age z-score >-3.0). MEDLINE, EMBASE, Global Health, CINAHL plus, ProQuest Dissertations and Thesis were systematically searched from 2001 to July 2014, manual reference searching of a birth cohort register (http://www.birthcohorts.net/) as well as papers identified in the search and selected journals was carried out. The database search yielded 9050 records, 275 English-language full-text articles were screened, but no studies were eligible, failing to meet the following criteria: comparison (213); exposure (14); population (3); relevant outcome (5); outcome before 24 months (9); insufficient information provided (30); plus one study was qualitative. Eight studies met the inclusion criterion of exclusive breastfeeding to 6 months, but did not meet the other inclusion criteria. The present study has revealed an important gap in the evidence on NCD prevention, and suggestions for addressing this evidence gap are provided.

Living with HIV, disclosure patterns and partnerships a decade after the introduction of HIV programmes in rural South Africa.

Prevention of mother-to-child Transmission and HIV Treatment programmes were scaled-up in resource-constrained settings over a decade ago, but there is still much to be understood about women's experiences of living with HIV and their HIV disclosure patterns. This qualitative study explored women's experiences of living with HIV, 6-10 years after being diagnosed during pregnancy. The area has high HIV prevalence, and an established HIV treatment programme. Participants were enrolled in a larger intervention, "Amagugu", that supported women (n = 281) to disclose their HIV status to their children. Post-intervention we conducted individual in-depth interviews with 20 randomly selected women, stratified by clinic catchment area, from the total sample. Interviews were entered into ATLAS.ti computer software for coding. Most women were living with their current sexual partner and half were still in a relationship with the child's biological father. Household exposure to HIV was high with the majority of women knowing at least one other HIV-infected adult in their household. Eighteen women had disclosed their HIV status to another person; nine had disclosed to their current partner first. Two main themes were identified in the analyses: living with HIV and the normalisation of HIV treatment at a family level; and the complexity of love relationships, in particular in long-term partnerships. A decade on, most women were living positively with HIV, accessing care, and reported experiencing little stigma. However, as HIV became normalised new challenges arose including concerns about access to quality care, and the need for family-centred care. Women's sexual choices and relationships were intertwined with feelings of love, loyalty and trust and the important supportive role played by partners and families was acknowledged, however, some aspects of living with HIV presented challenges including continuing to practise safe sex several years after HIV diagnosis.

HIV status, breastfeeding modality at 5 months and postpartum maternal weight changes over 24 months in rural South Africa.

OBJECTIVE: To determine the effect of infant feeding practices on postpartum weight change among HIV-infected and -uninfected women in South Africa. METHODS: In a non-randomised intervention cohort study of antiretroviral therapy-naïve women in South Africa, infants were classified as exclusive (EBF), mixed (MF) or non-breastfed (NBF) at each visit. We analysed infant feeding cumulatively from birth to 5 months using 24-hour feeding history (collected weekly for each of the preceding 7 days). Using generalised estimating equation mixed models, allowing for repeated measures, we compared postpartum weight change (kg) from the first maternal postpartum weight within the first 6 weeks (baseline weight) to each subsequent visit through 24 months among 2340 HIV-infected and -uninfected women with live births and at least two postpartum weight measurements. RESULTS: HIV-infected (-0.2 kg CI: -1.7 to 1.3 kg; P = 0.81) and -uninfected women (-0.5 kg; 95% CI: -2.1 to 1.2 kg; P = 0.58) had marginal non-significant weight loss from baseline to 24 months postpartum. Adjusting for HIV status, socio-demographic, pregnancy-related and infant factors, 5-month feeding modality was not significantly associated with postpartum weight change: weight change by 24 months postpartum, compared to the change in the reference EBF group, was 0.03 kg in NBF (95% CI: -2.5 to +2.5 kg; P = 0.90) and 0.1 kg in MF (95% CI: -3.0 to +3.2 kg; P = 0.78). CONCLUSION: HIV-infected and -uninfected women experienced similar weight loss over 24 months. Weight change postpartum was not associated with 5-month breastfeeding modality among HIV-infected and -uninfected women.

Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort.

BACKGROUND: Better understanding of drug resistance patterns in HIV-infected children on antiretroviral therapy (ART) is required to inform public health policies in high prevalence settings. The aim of this study was to characterise the acquired drug resistance in HIV-infected children failing first-line ART in a decentralised rural HIV programme. METHODS: Plasma samples were collected from 101 paediatric patients (≤15 yrs of age) identified as failing ART. RNA was extracted from the plasma, reverse transcribed and a 1.3 kb region of the pol gene was amplified and sequenced using Sanger sequencing protocols. Sequences were edited in Geneious and drug resistance mutations were identified using the RegaDB and the Stanford resistance algorithms. The prevalence and frequency of mutations were analysed together with selected clinical and demographic data in STATA v11. RESULTS: A total of 101 children were enrolled and 89 (88%) were successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the time of genotyping. The majority of patients on an NNRTI regimen (80%) had both nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 30.1% had one or more thymidine analogue mutation (TAM) and 6% had ≥3 TAMs. Only one child on a PI-based regimen harboured a major PI resistance mutation. CONCLUSIONS: Whilst the patterns of resistance were largely predictable, the few complex resistance patterns seen with NNRTI-based regimens and the absence of major PI mutations in children failing PI-based regimens suggest the need for wider access to genotypic resistance testing in this setting.

Elevated concentrations of milk ß2-microglobulin are associated with increased risk of breastfeeding transmission of HIV-1 (Vertical Transmission Study).

There is increasing evidence to support a relationship between human immunodeficiency virus (HIV-1) transmission through breastfeeding and milk host factors. We analyzed skim milk proteome to further determine the contribution of host factors to the risk of mother-to-child transmission of HIV-1. Quantitative mass spectrometry analysis was performed on nine case-control pairs of HIV+ transmitter/nontransmitter mothers, and specific biochemical assays on two selected proteins were assessed in an independent validation set of 127 samples. 33 identified proteins were differentially expressed between HIV+ transmitter and nontransmitter mothers. Among them, ß2-microglobulin was significantly higher in the maternal transmitter than in the nontransmitter groups (p value = 0.0007), and S100A9 was significantly higher in the early maternal transmitter cases (before 4 months of age) compared with the nontransmitters (p value = 0.004). ß2-Microglobulin correlated with milk and plasma HIV viral load and CD4+ cell count, whereas S100A9 correlated with the estimated timing of infection of the infant through breastfeeding. Finally, ß2-microglobulin concentration in milk could accurately predict the risk of HIV-1 postnatal transmission by breastfeeding (p value < 0.0001, log-rank test). In conclusion, milk ß2-microglobulin and S100A9 are host factors that are found to be associated with mother-to-child transmission of HIV-1.

Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa.

BACKGROUND: Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa. METHODS: Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001-2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors. RESULTS: Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06-1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91-1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18-3.81 and 2.77, 95% CI: 1.56-4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79-1.79 for 34-36 weeks and 1.31, 95% CI: 0.58-2.94 for <34 weeks). CONCLUSIONS: Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.

Human resources needs for universal access to antiretroviral therapy in South Africa: a time and motion study.

BACKGROUND: Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria. METHODS: We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year. RESULTS: For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/µl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$ 141 million. For universal treatment ('treatment as prevention'), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million). CONCLUSIONS: Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/µl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments.

Cumulative exposure to cell-free HIV in breast milk, rather than feeding pattern per se, identifies postnatally infected infants.

BACKGROUND: We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. METHODS: Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. RESULTS: Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ~15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). CONCLUSIONS: Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants.

Empowering parents for human immunodeficiency virus prevention: Health and sex education at home.

BACKGROUND: Improving health literacy amongst human immunodeficiency virus (HIV)-positive mothers could strengthen child and adolescent HIV prevention. The Amagugu intervention included health literacy materials to strengthen maternal communication and has demonstrated success in low-resource HIV-endemic settings. OBJECTIVES: Our aims were to (1) evaluate whether Amagugu materials improved health literacy leading to changes in parental behaviour towards communicating on topics such as HIV, health behaviours and sex education, and (2) explore what additional information and materials mothers would find helpful. METHOD: The Amagugu evaluation included 281 HIV-positive mothers and their HIV-uninfected children (6-10 years). Process evaluation data from exit interviews were analysed using content analysis and logistic regression techniques. RESULTS: Of 281 mothers, 276 (98.0%) requested more educational storybooks: 99 (35.2%) on moral development/future aspirations, 92 (32.7%) on general health, safety and health promotion, and 67 (23.8%) on HIV and disease management. Compared to baseline, mothers reported that the materials increased discussion on the risks of bullying from friends (150; 53.4%), teacher problems (142; 50.5%), physical abuse (147; 52.3%) and sexual abuse (126; 44.8%). Most mothers used the 'HIV Body Map' for health (274; 97.5%) and sex education (267; 95.0%). The use of a low-cost doll was reported to enhance mother-child communication by increasing mother-child play (264; 94.3%) and maternal attentiveness to the child's feelings (262; 93.6%). CONCLUSION: Parent-led health education in the home seems feasible, acceptable and effective and should be capitalised on in HIV prevention strategies. Further testing in controlled studies is recommended.

Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study.

BACKGROUND: Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding. METHODS: 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors. FINDINGS: 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birthweight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breastmilk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051). INTERPRETATION: The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.

Short communication: CD4 counts of HIV-infected pregnant women and their infected children--implications for PMTCT and treatment programmes.

A considerable proportion of pregnant women and their infected children are likely to be eligible for anti-retroviral treatment. The antenatal-postnatal divide needs to be bridged with respect to the follow-up of both HIV-infected women and their exposed infants.