Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding.

Subclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na+) and potassium (K+) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na + /K + ratio > 0.6) and severe SCM (Na + /K + ratio > 1) were 58.6% (95%CI: 52.7 - 64.5) and 27.8% (95%CI: 22.5 - 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 - 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 - 4.2). A Na+/K+ ratio > 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding.

Respiratory monitoring during neonatal resuscitation using a supraglottic airway device vs. a face mask.

OBJECTIVE: To evaluate the respiratory function of asphyxiated infants resuscitated with i-gel supraglottic airway (SGA) vs. face mask (FM) in a low-resource setting. METHODS: In this sub-study from the NeoSupra trial, respiratory function during the first 60 inflations was evaluated in 46 neonates (23 with SGA and 23 with FM) at the Mulago National Referral Hospital, Uganda. The primary outcome was the mask leak (%). The secondary outcomes included inspired (VTi) and expired (VTe) tidal volumes, and heart rate response to ventilation. RESULTS: Median mask leak was 40% (IQR 22-52) with SGA and 39% (IQR 26-62) with FM (p = 0.38). Median VTe was 7.8 ml/kg (IQR 5.6-10.2) with SGA and 7.3 ml/kg (IQR 4.8-11.9) with FM (p = 0.84), while median VTi was 15.4 ml/kg (IQR 11-4-17.6) with SGA and 15.9 ml/kg (IQR 9.0-22.6) with FM (p = 0.68). A shorter time was needed to achieve heart rate > 100 bpm in SGA (median 13 s IQR 9-15) with respect to FM arm (median 61, IQR 33-140) (p = 0.0002). CONCLUSION: Respiratory function was not statistically different between neonates resuscitated with SGA vs. FM. SGA was associated with faster heart rate recovery compared to FM in the subgroup of neonates with bradycardia. Further research is needed to investigate possible advantages of SGA on respiratory function at birth.

Mitochondrial DNA Instability Is Common in HIV-Exposed Uninfected Newborns.

Worldwide, one million HIV-exposed uninfected (HEU) children are born yearly, and chronic health impairments have been reported in these children. Mitochondrial DNA (mtDNA) instability and altered mtDNA content have been evidenced in these children, but an exhaustive characterization of altered mitochondrial genomes has never been reported. We applied deep mtDNA sequencing coupled to the deletion identification algorithm eKLIPse to the blood of HEU neonates (n = 32), which was compared with healthy controls (n = 15). Dried blood spots (DBS) from African HEU children were collected seven days after birth between November 2009 and May 2012. DBS from French healthy controls were collected at birth (or <3 days of life) in 2012 and in 2019. In contrast to the absence of mtDNA instability observed at the nucleotide level, we identified significant amounts of heteroplasmic mtDNA deletions in 75% of HEU children and in none of controls. The heteroplasmy rate of the 62 mtDNA deletions identified varied from 0.01% to up to 50%, the highest rates being broadly compatible with bioenergetic defect and clinical expression. mtDNA integrity is commonly affected in HEU neonates. The nature of the deletions suggests a mechanism related to aging or tumor-associated mtDNA instability. This child population may be at risk of additional mtDNA genetic alterations considering that they will be exposed to other mitotoxic drugs including antiretroviral or anti-tuberculosis treatment.

A North-South-South partnership in higher education to develop health research capacity in the Democratic Republic of the Congo: the challenge of finding a common language.

BACKGROUND: Globally, increasing numbers of higher education institutions (HEIs) in non-English-speaking countries have adopted English as a medium of instruction (EMI), because of the perception that this provides opportunities to attract high-calibre students and academic staff, and engage with the international research community. We report an evaluation of a North-South-South collaboration to develop health research capacity in the Democratic Republic of the Congo (DRC) by establishing a postgraduate programme in nutritional epidemiology at the Kinshasa School of Public Health (KSPH), where EMI was adopted. We report experiences and perceptions of stakeholders, facilitators and students about using EMI. METHODS: In-depth qualitative interviews were conducted between October and December 2019 among convenience sampled stakeholders (8), facilitators (11) and students (12) involved in the programme from all three partner institutions (University of Kinshasa; University of KwaZulu-Natal, South Africa; University of Bergen, Norway). Interviews were conducted in participants' language of preference (English or French), audio-recorded, transcribed verbatim and translated into English when required. Analysis employed a thematic approach. RESULTS: Most participants viewed EMI positively, reporting that studying in English created opportunities to access relevant literature, improve interactions with the scientific community and advance their careers. As a result of adopting EMI, some students had opportunities to present research findings at international conferences and publish their research in English. English-speaking researchers from partner institutions were able to participate in supervision of students' research. However, inadequate English competency, particularly among students, was challenging, with some students reporting being unable to understand or interact in class, which negatively affected their academic performance. Further, EMI created barriers at KSPH among academic staff who were not proficient in English, leading to poor participation among non-English-speaking staff and lack of integration with other postgraduate programmes. Participants suggested additional English language support for EMI. CONCLUSION: Partnerships between HEIs could be a powerful tool to develop research capacity in low-income countries in line with United Nations Sustainable Development Goals. EMI could be a solution to language barriers faced by many such partnerships, but wide-ranging support to develop English proficiency among staff and students is essential to ensure that the challenges do not outweigh the benefits.

Where Are the Newly Diagnosed HIV Positives in Kenya? Time to Consider Geo-Spatially Guided Targeting at a Finer Scale to Reach the "First 90".

Background: The UNAIDS 90-90-90 Fast-Track targets provide a framework for assessing coverage of HIV testing services (HTS) and awareness of HIV status - the "first 90." In Kenya, the bulk of HIV testing targets are aligned to the five highest HIV-burden counties. However, we do not know if most of the new HIV diagnoses are in these five highest-burden counties or elsewhere. Methods: We analyzed facility-level HTS data in Kenya from 1 October 2015 to 30 September 2016 to assess the spatial distribution of newly diagnosed HIV-positives. We used the Moran's Index (Moran's I) to assess global and local spatial auto-correlation of newly diagnosed HIV-positive tests and Kulldorff spatial scan statistics to detect hotspots of newly diagnosed HIV-positive tests. For aggregated data, we used Kruskal-Wallis equality-of-populations non-parametric rank test to compare absolute numbers across classes. Results: Out of 4,021 HTS sites, 3,969 (98.7%) had geocodes available. Most facilities (3,034, 76.4%), were not spatially autocorrelated for the number of newly diagnosed HIV-positives. For the rest, clustering occurred as follows; 438 (11.0%) were HH, 66 (1.7%) HL, 275 (6.9%) LH, and 156 (3.9%) LL. Of the HH sites, 301 (68.7%) were in high HIV-burden counties. Over half of 123 clusters with a significantly high number of newly diagnosed HIV-infected persons, 73(59.3%) were not in the five highest HIV-burden counties. Clusters with a high number of newly diagnosed persons had twice the number of positives per 1,000,000 tests than clusters with lower numbers (29,856 vs. 14,172). Conclusions: Although high HIV-burden counties contain clusters of sites with a high number of newly diagnosed HIV-infected persons, we detected many such clusters in low-burden counties as well. To expand HTS where most needed and reach the "first 90" targets, geospatial analyses and mapping make it easier to identify and describe localized epidemic patterns in a spatially dispersed epidemic like Kenya's, and consequently, reorient and prioritize HTS strategies.

Growth, clinical and neurodevelopmental outcomes at school age are similar for children who received 1-year lamivudine or lopinavir/ritonavir HIV prophylaxis in early life.

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

Clinical and Biological Factors Associated With Early Epstein-Barr Virus Infection in Human Immunodeficiency Virus-Exposed Uninfected Infants in Eastern Uganda.

BACKGROUND: Immune control of Epstein-Barr virus (EBV) infection is impaired in individuals with HIV. We explored maternal factors associated with EBV acquisition in HIV-exposed uninfected (HEU) infants and the relationship between EBV infection and serious adverse events (SAEs) during the first year of life. METHODS: 201 HEU infants from Uganda enrolled in the ANRS 12174 trial were tested for antiviral capsid antigen (anti-VCA) antibodies at week 50. Date of infection was estimated by testing EBV DNA at weeks 1, 6, 14, 26, 38, and 50 postpartum on dried blood spots. RESULTS: Eighty-seven (43%) infants tested positive for anti-VCA IgG at week 50. Among the 59 infants positive for EBV DNA, 25% were infected within the first 26 weeks. Almost half (12%) were infected before week 14. Shedding of EBV in breast milk was associated with EBV DNA in maternal plasma (P = .009), HIV RNA detection (P = .039), and lower CD4 count (P = .001) and correlated with plasma EBV DNA levels (P = .002). EBV infant infection at week 50 was associated with shedding of EBV in breast milk (P = .009) and young maternal age (P = .029). Occurrence of a clinical SAE, including malaria and pneumonia, was associated with higher levels of EBV DNA in infants (P = .010). CONCLUSIONS: By assessing EBV infection in HEU infants we observed that infection during the first year is determined by HIV and EBV maternal factors and that EBV DNA levels were higher among infants with clinical SAEs. CLINICAL TRIALS REGISTRATION: NCT00640263.

An educational intervention to update health workers about HIV and infant feeding.

Clinical guidelines are used to translate research findings into evidence-based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV-exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team-based, mentoring programme developed to update HWs on these guidelines. The intervention was underpinned by strong theoretical frameworks and aimed to improve HWs' attitudes, knowledge, confidence, and skills about breastfeeding in the context of HIV. On-site workshops and clinical mentoring used interactive participatory methods and a simple low-tech approach, guided by participants' self-reported knowledge gaps. Workshops were conducted at 24 participating clinics over three sessions, each lasting 1-2 hr. Evaluation data were collected using a self-administered questionnaire. Of 303 participating HWs, 249/303 (82.2%) attended all workshops. Achieving high workshop attendance was challenging and "catch-up" sessions were required to achieve good coverage. Common knowledge gaps identified included antiretroviral therapy adherence monitoring during breastfeeding and management of viral load results (173 participants), management of breast conditions (79), and advice about expressing and storing breastmilk (64). Most participants reported all their knowledge gaps were addressed and anticipated that their practice would change. We describe a feasible, sustainable approach to updating HWs on HIV and infant feeding guidelines and improving skills in breastfeeding counselling in resource-constrained settings. This approach could be adapted to other topics and, with further evaluation, implemented at scale using existing resources.

Comparison of 6-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART: Results from an observational prospective cohort study.

BACKGROUND: Lifelong antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) and improves maternal health. Data on the outcomes of HIV-exposed infants (HEI) compared to their unexposed counterparts in the era of universal ART is limited. We compared birth and 6-week outcomes among infants born to HIV-positive and HIV-negative women in Lesotho. METHODS: 941 HIV-negative and 653 HIV-positive pregnant women were enrolled in an observational cohort to evaluate the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) program after implementation of universal maternal ART in 14 health facilities. Pregnancy, delivery, birth, and 6-week data were collected through participant interviews and medical record review. DNA PCR testing for HEI was conducted within 2 weeks of birth and at around 6 weeks of age. Data were analysed to estimate the distribution of birth outcomes, mortality, HIV transmission and HIV-free survival at 6 weeks. RESULTS: HIV-positive women were older (mean age of 28.7 vs. 24.4 years) and presented for antenatal care earlier (mean gestational age of 23.0 weeks vs 25.3 weeks) than HIV-negative women. Prematurity was more frequent among HEI, 7.8% vs. 3.6%. There was no difference in rates of congenital anomalies between HEI (1.0%) and HIV-unexposed infants (HUI) (0.6%). Cumulative HIV transmission was 0.9% (N = 4/431) (95% CI:0.25-2.36) at birth and 1.0% (N = 6/583) (95% CI:0.38-2.23) at 6 weeks. Overall mortality, including stillbirths, was 5.2% and 6.0% by 6 weeks for HUI and HEI respectively. Among liveborn infants, 6-week HIV-free survival for HEI was 95.6% (95% CI:93.7-97.1) compared to 96.8% (95% CI:95.4-97.9) survival for HUI. CONCLUSIONS: Implementation of universal maternal ART lowers MTCT at 6 weeks of age with no differences in congenital anomalies or early mortality between HIV exposed Infants and HIV unexposed infants. However, HIV exposed infants continue to have high rates of prematurity despite improved maternal health on ART.

The cost-effectiveness of incentive-based active case finding for tuberculosis (TB) control in the private sector Karachi, Pakistan.

BACKGROUND: In Asia, over 50% of patients with symptoms of tuberculosis (TB) access health care from private providers. These patients are usually not notified to the National TB Control Programs, which contributes to low notification rates in many countries. METHODS: From January 1, 2011 to December 31, 2012, Karachi's Indus Hospital - a private sector partner to the National TB Programme - engaged 80 private family clinics in its catchment area in active case finding using health worker incentives to increase notification of TB disease. The costs incurred were estimated from the perspective of patients, health facility and the program providing TB services. A Markov decision tree model was developed to calculate the cost-effectiveness of the active case finding as compared to case detection through the routine passive TB centers. Pakistan has a large private health sector, which can be mobilized for TB screening using an incentivized active case finding strategy. Currently, TB screening is largely performed in specialist public TB centers through passive case finding. Active and passive case finding strategies are assumed to operate independently from each other. RESULTS: The incentive-based active case finding program costed USD 223 per patient treated. In contrast, the center based non-incentive arm was 23.4% cheaper, costing USD 171 per patient treated. Cost-effectiveness analysis showed that the incentive-based active case finding program was more effective and less expensive per DALY averted when compared to the baseline passive case finding as it averts an additional 0.01966 DALYs and saved 15.74 US$ per patient treated. CONCLUSION: Both screening strategies appear to be cost-effective in an urban Pakistan context. Incentive driven active case findings of TB in the private sector costs less and averts more DALYs per health seeker than passive case finding, when both alternatives are compared to a common baseline situation of no screening.

Conventional early infant diagnosis in Lesotho from specimen collection to results usage to manage patients: Where are the bottlenecks?

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade. METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means (with 95% CI) were calculated and compared by region using linear mixed models. RESULTS: 1,187 individual infant records from 25 facilities were reviewed. Overall, early infant diagnosis turnaround time was 61.7 days (95%CI: 55.3-68.7). Mean time from specimen collection to district laboratory was 14 days (95%CI: 12.1-16.1); from district to central laboratory, 2 days (95%CI 0.8-5.2); results from central laboratory to district hospital, 23.3 days (95%CI: 18.7-29.0); from district hospital to health facility, 3.2 days (95%CI 1.9-5.5); and from health facility to caregiver, 10.4 days (95%CI, 7.9-13.5). Mean times from specimen transfer to the central laboratory and for result transfer from central laboratory to district hospital were significantly shorter in the Lowlands Region (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [P = 0.030] and 34.3 days [P = 0.0099]. Turnaround time from blood draw to receipt of results was significantly shorter for HIV infected infants compared to HIV uninfected infants [p = 0.0036] at an average of 47.1 days (95%CI: 38.9-56.9) and 62 days (95%CI: 55.9-68.7) respectively. Of 47 HIV-infected infants, 36 were initiated on antiretroviral therapy at an average of 1.3 days (95%CI: 0.3, 5.7) after caregiver received the result. CONCLUSION: HIV-infected infants received results earlier and were rapidly initiated on antiretroviral therapy once the result was delivered to caregiver. However, average early infant diagnosis turnaround time was two months; the longest period of delay was transfer of results from central laboratory to district hospital. Turnaround time of results based on geographical regions or between hospitals and health centres varied but did not reach statistical significance.

Echoes of old HIV paradigms: reassessing the problem of engaging men in HIV testing and treatment through women's perspectives.

BACKGROUND: With the introduction of 2016 World Health Organization guidelines recommending universal antiretroviral therapy (ART), there has been increased recognition of the lack of men engaging in HIV testing and treatment. Studies in sub-Saharan Africa indicate there have been challenges engaging men in HIV testing and HIV-positive men into treatment. METHODS: This qualitative study explored women's perspective of their male partner's attitudes towards HIV and ART and how it shapes woman's experience with ART. Data were collected through in-depth interviews and focus group discussions with HIV-positive pregnant and postpartum women on Option B+ and health care workers in Malawi and Zimbabwe. In Malawi, 19 in-depth interviews and 12 focus group discussions were conducted from September-December 2013. In Zimbabwe, 15 in-depth interviews and 21 focus-group discussions were conducted from July 2014-March 2014. RESULTS: The findings highlighted that many men discourage their partners from initiating or adhering to ART. One of the main findings indicated that despite the many advancements in HIV care and ART regimens, there are still many lingering negative beliefs about HIV and ART from the earlier days of the epidemic. In addition to existing theories explaining men's resistance to/absence in HIV testing and treatment as a threat to their masculinity or because of female-focused health facilities, this paper argues that men's aversion to HIV may be a result of old beliefs about HIV and ART which have not been addressed. CONCLUSIONS: Due to lack of accurate and up to date information about HIV and ART, many men discourage their female partners from initiating and adhering to ART. The effect of lingering and outdated beliefs about HIV and ART needs to be addressed through strengthened communication about developments in HIV care and treatment. Universal ART offers a unique opportunity to curb the epidemic, but successful implementation of these new guidelines is dependent on ART initiation and adherence by both women and men. Strengthening men's understanding about HIV and ART will greatly enhance women's ability to initiate and adhere to ART and improve men's health.

Early versus late BCG vaccination in HIV-1-exposed infants in Uganda: study protocol for a randomized controlled trial.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants. METHODS: This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1ß, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda. DISCUSSION: A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02606526 . Registered on 12 November 2015.

Explaining socioeconomic inequalities in exclusive breast feeding in Norway.

BACKGROUND AND OBJECTIVE: In high-income countries, lower socioeconomic position is associated with lower rates of breast feeding, but it is unclear what factors explain this inequality. Our objective was to examine the association between socioeconomic position and exclusive breast feeding, and to explore whether socioeconomic inequality in exclusive breast feeding could be explained by other sociodemographic characteristics, for example, maternal age and parity, smoking habits, birth characteristics, quality of counselling and breastfeeding difficulties. METHODS: We used data from a questionnaire sent to mothers when their infants were five completed months as part of a trial of a breastfeeding intervention in Norway. We used maternal education as an indicator of socioeconomic position. Analyses of 1598 mother-infant pairs were conducted using logistic regression to assess explanatory factors of educational inequalities in breast feeding. RESULTS: Socioeconomic inequalities in exclusive breast feeding were present from the beginning and persisted for five completed months, when 22% of the most educated mothers exclusively breast fed compared with 7% of the least educated mothers: OR 3.39 (95% CI 1.74 to 6.61). After adjustment for all potentially explanatory factors, the OR was reduced to 1.49 (95% CI 0.70 to 3.14). This decrease in educational inequality seemed to be mainly driven by sociodemographic factors, smoking habits and breastfeeding difficulties, in particular perceived milk insufficiency. CONCLUSIONS: Socioeconomic inequalities in exclusive breast feeding at 5 months were largely explained by sociodemographic factors, but also by modifiable factors, such as smoking habits and breastfeeding difficulties, which can be amenable to public health interventions. TRIAL REGISTRATION NUMBER: NCT01025362.

Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding.

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy: A Retrospective Cohort Study from Goma, the Democratic Republic of Congo.

BACKGROUND: Anaemia is associated with adverse outcomes including early death in the first year of antiretroviral therapy (ART). This study reports on the factors associated with persistent anaemia among HIV-infected patients initiating ART in the Democratic Republic of Congo (DR Congo). METHODS: We conducted a retrospective cohort study and analyzed data from patients receiving HIV care between January 2004 and December 2012 at two major hospitals in Goma, DR Congo. Haemoglobin concentrations of all patients on ART regimen were obtained prior to and within one year of ART initiation. A logistic regression model was used to identify the predictors of persistent anaemia after 12 months of ART. RESULTS: Of 756 patients, 69% of patients were anaemic (IC95%: 65.7-72.3) at baseline. After 12 months of follow up, there was a 1.2 g/dl average increase of haemoglobin concentration (P < 0.001) with differences depending on the therapeutic regimen. Patients who received zidovudine (AZT) gained less than those who did not receive AZT (0.99 g/dl vs 1.33 g/dl; p< 0.001). Among 445 patient who had anaemia at the beginning, 33% (147/445) had the condition resolved. Among patients with anaemia at ART initiation, those who did not receive cotrimoxazole prophylaxis before starting ART(AOR 3.89; 95% CI 2.09-7.25; P < 0.001) and a AZT initial regimen (AOR 2.19; 95% CI 1.36-3.52; P < 0.001) were significantly at risk of persistent anaemia. CONCLUSIONS: More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma.

Dietary behaviour and parental socioeconomic position among adolescents: the German Health Interview and Examination Survey for Children and Adolescents 2003-2006 (KiGGS).

BACKGROUND: The positive association between parental socioeconomic position (PSEP) and health among adolescents may be partly explained by dietary behaviour. We investigated the associations between fruit intake, vegetable intake, energy-dense food intake, the Healthy Nutrition Score for Kids and Youth (HuSKY) and parental education in a nationwide, cluster-randomized sample of adolescents in Germany. METHODS: The German Health Interview and Examination Survey for Children and Adolescents 2003-2006 (KiGGS) included 17,641 individuals aged 0-17 years and their parents. Complete information on relevant variables was available for 6359 individuals in the 11-17 age group. The associations between nutrition indicators and parental education were analysed separately for boys and girls, using multivariate logistic regression analysis. Odds ratios (ORs) adjusted for age, region, income, occupation, physical activity and weight status related variables, were calculated for the associations between parental education and nutrition indicators. RESULTS: After full adjustment, higher parental education level was associated with lower energy-dense food intake - with an OR of 1.3 (95 % CI 1.0-1.7) for boys with secondary educated parents and 1.8 (1.4-2.3) for boys with tertiary educated parents compared to boys with primary educated parents; the corresponding ORs for girls were 1.2 (0.9-1.5) and 1.6 (1.2-2.2). Higher parental education was associated with higher fruit intake - with an OR of 1.3 (1.0-1.7) for boys with secondary educated parents and 2.0 (1.5-2.7) for boys with tertiary educated parents compared to boys with primary educated parents; the corresponding ORs for girls were 1.0 (0.8-1.4) and 1.5 (1.0-2.1). Among boys and girls with tertiary educated parents compared to those with primary educated parents an OR of 1.3 (CI boys: 1.0-1.7, CI girls: 1.0-1.6) was observed for high vegetable intake. Among boys with tertiary educated parents compared to boys with primary educated parents an OR of 1.6 (1.2-2.2) was observed for a high HuSKY; the corresponding OR for girls was 1.5 (1.1-1.9). CONCLUSIONS: A high PSEP is associated with consumption of less energy-dense food, more fruits and vegetables and more favourable overall dietary behaviour. Preferably school-based interventions are needed to promote healthy dietary behaviour among German adolescents and a special effort is needed to reach adolescents from low-PSEP families.

Severe events in the first 6 months of life in a cohort of HIV-unexposed infants from South Africa: effects of low birthweight and breastfeeding status.

OBJECTIVE: To report on risk factors for severe events (hospitalisation or infant death) within the first half of infancy amongst HIV-unexposed infants in South Africa. METHODS: South African data from the multisite community-based cluster-randomised trial PROMISE EBF promoting exclusive breastfeeding in three sub-Saharan countries from 2006 to 2008 were used. The South African sites were Paarl in the Western Cape Province, and Umlazi and Rietvlei in KwaZulu-Natal. This analysis included 964 HIV-negative mother-infant pairs. Data on severe events and infant feeding practices were collected at 3, 6, 12 and 24 weeks post-partum. We used a stratified extended Cox model to examine the association between the time to the severe event and covariates including birthweight, with breastfeeding status as a time-dependent covariate. RESULTS: Seventy infants (7%) experienced a severe event. The median age at first hospitalisation was 8 weeks, and the two main reasons for hospitalisation were cough and difficult breathing followed by diarrhoea. Stopping breastfeeding before 6 months (HR 2.4; 95% CI 1.2-5.1) and low birthweight (HR 2.4; 95% CI 1.3-4.3) were found to increase the risk of a severe event, whilst maternal completion of high school education was protective (HR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: A strengthened primary healthcare system incorporating promotion of breastfeeding and appropriate caring practices for low birthweight infants (such as kangaroo mother care) are critical. Given the leading reasons for hospitalisation, early administration of oral rehydration therapy and treatment of suspected pneumonia are key interventions needed to prevent hospitalisation in young infants.