Optimised prevention of postnatal HIV transmission in Zambia and Burkina Faso (PROMISE-EPI): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission. METHODS: We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438). FINDINGS: Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30·6 years (IQR 26·0-34·7), 1480 (98·4%) of 1504 were receiving ART, and 169 (11·5%) of 1466 had a viral load ≥1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0·19 per 100 person-years (95% CI 0·005-1·04) in the intervention group and 1·16 per 100 person-years (0·43-2·53) in the control group, which did not reach statistical significance (p=0·066). HIV-free survival and serious adverse events were similar in both groups. INTERPRETATION: Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination. FUNDING: The EDCTP2 programme with the support of the UK Department of Health & Social Care.

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial.

BACKGROUND: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV. METHODS: Two bNAbs, CAP256V2LS and VRC07-523LS, will be assessed in a sequential and randomized phase I, single-site, single-blind, dose-finding trial. We aim to investigate the 28-day safety and pharmacokinetics (PK) profile of incrementally higher doses of these bNAbs in breastfeeding HIV-1 exposed born without HIV neonates alongside standard of care antiretroviral (ARV) medication to prevent (infants) or treat (mothers) HIV infection. The trial design includes 3 steps and 7 arms (1, 2, 3, 4, 5, 6 and 6b) with 8 infants in each arm. The first step will evaluate the safety and PK profile of the bNAbs when given alone as a single subcutaneous (SC) administration at increasing mg/kg body weight doses within 96 h of birth: arms 1, 2 and 3 at doses of 5, 10, and 20 mg/kg of CAP256V2LS, respectively; arms 4 and 5 at doses of 20 and 30 mg/kg of VRC07-523LS, respectively. Step two will evaluate the safety and PK profile of a combination of the two bNAbs administered SC at fixed doses within 96 h of birth. Step three will evaluate the safety and PK profile of the two bNAbs administered SC in combination at fixed doses, after 3 months. Arms 1 and 6 will follow sequential recruitment, whereas randomization will occur sequentially between arms (a) 2 & 4 and (b) 3 & 5. Before each randomization, a safety pause will allow review of safety data of the preceding arms. DISCUSSION: The results of this trial will guide further studies on bNAbs to prevent breast milk transmission of HIV. PROTOCOL VERSION: Version 4.0 dated 15 March 2024. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR): PACTR202205715278722, 21 April 2022; South African National Clinical Trial Registry (SANCTR): DOH-27-062022-6058.

A Randomized Trial of Laryngeal Mask Airway in Neonatal Resuscitation.

BACKGROUND: Face-mask ventilation is the most common resuscitation method for birth asphyxia. Ventilation with a cuffless laryngeal mask airway (LMA) has potential advantages over face-mask ventilation during neonatal resuscitation in low-income countries, but whether the use of an LMA reduces mortality and morbidity among neonates with asphyxia is unknown. METHODS: In this phase 3, open-label, superiority trial in Uganda, we randomly assigned neonates who required positive-pressure ventilation to be treated by a midwife with an LMA or with face-mask ventilation. All the neonates had an estimated gestational age of at least 34 weeks, an estimated birth weight of at least 2000 g, or both. The primary outcome was a composite of death within 7 days or admission to the neonatal intensive care unit (NICU) with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization. RESULTS: Complete follow-up data were available for 99.2% of the neonates. A primary outcome event occurred in 154 of 563 neonates (27.4%) in the LMA group and 144 of 591 (24.4%) in the face-mask group (adjusted relative risk, 1.16; 95% confidence interval [CI], 0.90 to 1.51; P = 0.26). Death within 7 days occurred in 21.7% of the neonates in the LMA group and 18.4% of those in the face-mask group (adjusted relative risk, 1.21; 95% CI, 0.90 to 1.63), and admission to the NICU with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization occurred in 11.2% and 10.1%, respectively (adjusted relative risk, 1.27; 95% CI, 0.84 to 1.93). Findings were materially unchanged in a sensitivity analysis in which neonates with missing data were counted as having had a primary outcome event in the LMA group and as not having had such an event in the face-mask group. The frequency of predefined intervention-related adverse events was similar in the two groups. CONCLUSIONS: In neonates with asphyxia, the LMA was safe in the hands of midwives but was not superior to face-mask ventilation with respect to early neonatal death and moderate-to-severe hypoxic-ischemic encephalopathy. (Funded by the Research Council of Norway and the Center for Intervention Science in Maternal and Child Health; NeoSupra ClinicalTrials.gov number, NCT03133572.).

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Under-five mortality in the Democratic Republic of the Congo: secondary analyses of survey and conflict data by province.

Objective: To compare coverage of key child health policy indicators across provinces and to explore their association with under-five mortality and level of conflict in the Democratic Republic of the Congo. Methods: We made a secondary analysis of nationally representative data from 1380 health facilities and 20 792 households in 2017-2018. We analysed provincial-level data on coverage of 23 different indicators for improving common causes of childhood mortality, combined into mean scores for: newborn health, pneumonia, diarrhoea, malaria and safe environment. Using negative binomial regression we compared the scores with provincial-level under-five mortality. With binary logistic regression at the individual level we compared indicators (outcome) with living in a conflict-affected province (exposure). Findings: All grouped coverage scores demonstrated large ranges across the 26 provinces: newborn health: 20% to 61%; pneumonia: 26% to 86%; diarrhoea: 25% to 63%; malaria: 22% to 53%; and safe environment: 4% to 53%. The diarrhoea score demonstrated the strongest association with under-five mortality (adjusted coefficient: -0.026; 95% confidence interval: -0.045 to -0.007). Conflict-affected provinces had both the highest as well as the lowest mortality rates and indicator coverages. The odds of coverage were higher in conflict-affected provinces for 13 out of 23 indicators, whereas in provinces unaffected by conflict only one indicator had higher odds of coverage. Conclusion: Conflict alone is a poor predictor for child health. Ensuring that children in unaffected provinces are not neglected while addressing the needs of the most vulnerable in conflict settings is important. Prevent, protect and treat strategies for diarrhoeal disease could help improve equity in child survival.

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.

Incidence of home delivery among women living with HIV in Lira, Northern Uganda: a prospective cohort study.

BACKGROUND: Home delivery has been associated with mother-to-child transmission of HIV and remains high among HIV-infected women. Predictors for home delivery in the context of HIV have not been fully studied and understood in Northern Uganda. We therefore aimed to find out the incidence and risk factors for home delivery among women living with HIV in Lira, Northern Uganda. METHODS: This prospective cohort study was conducted between August 2018 and January 2020 in Lira district, Northern Uganda. A total of 505 HIV infected women receiving antenatal care at Lira regional referral hospital were enrolled consecutively and followed up at delivery. We used a structured questionnaire to obtain data on exposures which included: socio-demographic, reproductive-related and HIV-related characteristics. Data was analysed using Stata version 14.0 (StataCorp, College Station, Texas, U.S.A.). We estimated adjusted risk ratios using Poisson regression models to ascertain risk factors for the outcome of interest which was home delivery (which is delivering an infant outside a health facility setting under the supervision of a non-health worker). RESULTS: The incidence of home delivery among women living with HIV was 6.9% (95%CI: 4.9-9.5%). Single women were more likely to deliver at home (adjusted risk ratio = 4.27, 95%CI: 1.66-11). Women whose labour started in the night (night time onset of labour ARR = 0.39, 95%CI: 0.18-0.86) and those that were adherent to their ART (ARR = 0.33, 95%CI: 0.13-0.86) were less likely to deliver at home. CONCLUSION: Home delivery remains high among women living with HIV especially those that do not have a partner. We recommend intensified counselling on birth planning and preparedness in the context of HIV and PMTCT especially for women who are: separated, divorced, widowed or never married and those that are not adherent to their ART.

Health care provided to recent asylum-seeking and non-asylum-seeking pediatric patients in 2016 and 2017 at a Swiss tertiary hospital - a retrospective study.

BACKGROUND: Asylum-seeking children represent an increasing and vulnerable group of patients whose health needs are largely unmet. Data on the health care provision to asylum-seeking children in European contexts is scarce. In this study we compare the health care provided to recent asylum-seeking and non-asylum-seeking children at a Swiss tertiary hospital. METHODS: We performed a cross-sectional retrospective study in a pediatric tertiary care hospital in Basel, Switzerland. All patients and visits from January 2016 to December 2017 were identified, using administrative and medical electronic health records. The asylum-seeking status was systematically assessed and the patients were allocated accordingly in the two study groups. RESULTS: A total of 202,316 visits by 55,789 patients were included, of which asylum-seeking patients accounted for 1674 (1%) visits by 439 (1%) individuals. The emergency department recorded the highest number of visits in both groups with a lower proportion in asylum-seeking compared to non-asylum-seeking children: 19% (317/1674) and 32% (64,315/200,642) respectively. The median number of visits per patient was 1 (IQR 1-2) in the asylum-seeking and 2 (IQR 1-4) in the non-asylum-seeking children. Hospital admissions were more common in asylum-seeking compared to non-asylum-seeking patients with 11% (184/1674) and 7% (14,692/200,642). Frequent visits (> 15 visits per patient) accounted for 48% (807/1674) of total visits in asylum-seeking and 25% (49,886/200,642) of total visits in non-asylum-seeking patients. CONCLUSIONS: Hospital visits by asylum-seeking children represented a small proportion of all visits. The emergency department had the highest number of visits in all patients but was less frequently used by asylum-seeking children. Frequent care suggests that asylum-seeking patients also present with more complex diseases. Further studies are needed, focusing on asylum-seeking children with medical complexity.

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.

Establishing a postgraduate programme in nutritional epidemiology to strengthen resource capacity, academic leadership and research in the democratic republic of Congo.

BACKGROUND: Low- and Middle-income countries (LMIC) face considerable health and nutrition challenges, many of which can be addressed through strong academic leadership and robust research translated into evidence-based practice. A North-South-South partnership between three universities was established to implement a master's programme in nutritional epidemiology at the Kinshasa School of Public Health (KSPH), Democratic Republic of Congo (DRC). The partnership aimed to develop academic leadership and research capacity in the field of nutrition in the DRC. In this article we describe the educational approach and processes used, and discuss successes, challenges, and lessons learned. METHODS: Self-administered questionnaires, which included both open and closed questions, were sent to all graduates and students on the master's programme to explore students' experiences and perceptions of all aspects of the educational programme. Quantitative data was analysed using frequencies, and a thematic approach was used to analyse responses to open-ended questions. RESULTS: A two-year master's programme in Nutritional Epidemiology was established in 2014, and 40 students had graduated by 2020. Key elements included using principles of authentic learning, deployment of students for an internship at a rural residential research site, and support of selected students with bursaries. Academic staff from all partner universities participated in teaching and research supervision. The curriculum and teaching approach were well received by most students, although a number of challenges were identified. Most students reported benefits from the rural internship experience but were challenged by the isolation of the rural site, and felt unsupported by their supervisors, undermining students' experiences and potentially the quality of the research. Financial barriers were also reported as challenges by students, even among those who received bursaries. CONCLUSION: The partnership was successful in establishing a Master Programme in Nutritional Epidemiology increasing the number of nutrition researchers in the DRC. This approach could be used in other LMIC settings to address health and nutrition challenges.

Lopinavir-Ritonavir Impairs Adrenal Function in Infants.

BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.

Preventable admissions and emergency-department-visits in pediatric asylum-seeking and non-asylum-seeking patients.

BACKGROUND: Migrant health has become an essential part of public health. According to the World Health Organization, many health systems in Europe have not yet adapted adequately to the needs of asylum-seekers, which might result in untimely and inefficient health care for asylum-seeking patients. The aim of this study was to assess the number of preventable hospital admissions and emergency department visits in asylum-seeking and non-asylum-seeking pediatric patients. METHODS: This is a retrospective, hospital-based study. The study was done at the University Children's Hospital Basel in Switzerland. Patients admitted or presenting to the emergency department were included and split into the groups of asylum-seeking and non-asylum-seeking patients. All admissions and emergency-department visits were extracted from the administrative electronic health records from 1st Jan 2016-31st Dec 2017. The main outcome was the proportion of admissions due to ambulatory-care-sensitive conditions (which refer to conditions for which admission can be prevented by early interventions in primary care) in asylum-seeking and non-asylum-seeking patients. Ambulatory-care-sensitive conditions were defined by a validated list of ICD-10 codes. The secondary objective was to assess the number of preventable emergency-department visits by asylum-seeking patients defined as proportion of visits with a non-urgent triage score. RESULTS: A total of 75'199 hospital visits were included, of which 63'405 were emergency department visits and 11'794 were admissions. Ambulatory-care-sensitive conditions accounted for 12.1% (18/149) of asylum-seeking and 10.9% (1270/11645) of non-asylum seeking patients' admissions. Among the emergency department visits by asylum-seeking patients, non-urgent conditions accounted for 82.2% (244/297). CONCLUSIONS: Admissions due to ambulatory-care-sensitive conditions are comparable in asylum-seeking and non-asylum-seeking children, suggesting few delayed presentations to ambulatory care facilities. Strategies to prevent non-urgent visits at pediatric emergency department facilities are needed.

"The cord is the child": meanings and practices related to umbilical cord care in Central Uganda.

BACKGROUND: Infections account for a quarter of all newborn deaths and the umbilical cord has been identified as a major route of newborn infections. OBJECTIVE: To explore the meanings and practices related to the umbilical cord among caretakers of newborns in central Uganda. METHODS: This was a qualitative study, designed to inform the design, and interpretation of a randomized controlled trial assessing the effectiveness of chlorhexidine use for the umbilical cord. We conducted 22 in-depth interviews exploring umbilical cord care practices among ten mothers, four health workers, five traditional birth attendants, and three men. We also conducted three focus group discussions with young mothers and elderly women. We used qualitative content analysis to analyze our findings and we borrow upon Mary Douglas' concepts of dirt to present our findings. RESULTS: The umbilical cord had a symbolic position in newborn care. The way it was perceived and handled had far reaching consequences for the survival and wellbeing of the baby. The umbilical cord was a centre of anxiety, a possible gate to illness, a test of fatherhood and a signifier of parental responsibility. Hence, the umbilical cord and the way it was cared for played a part in the present and future survival of the baby, as well as the survival and wellbeing of the household. Persons other than the mother such as older female relatives were very influential in the care of the umbilical cord. CONCLUSIONS: The umbilical cord carried symbolic meanings, which extended beyond the newborn and the newborn period, and in turn influenced the various practices of umbilical cord care. The important position of the cord in local newborn care practices should be recognized and taken into consideration when scaling up newborn care interventions in the country.

Breastfeeding advice for reality: Women's perspectives on primary care support in South Africa.

Breastfeeding education and support are critical health worker skills. Confusion surrounding infant feeding advice linked to the HIV epidemic has reduced the confidence of health workers to support breastfeeding. High antiretroviral therapy coverage of breastfeeding women living with HIV, and an Infant Feeding policy supportive of breastfeeding, now provides an opportunity to improve breastfeeding practices. Challenges remain in restoring health worker confidence to support breastfeeding. This qualitative study presents findings from focus group discussions with mothers of young infants, exploring their experiences of health worker breastfeeding counselling and support. Analysis followed the thematic framework approach. Six researchers reviewed the transcripts, coded them independently, then jointly reviewed the codes, and agreed on a working analytical framework. Although mothers received antenatal breastfeeding messages, these appeared to focus rigidly on the importance of exclusivity. Mothers described receiving some practical support with initiation of breastfeeding after delivery, but support and advice for post-natal breastfeeding challenges were often incorrect or absent. The support also ignored the context in which women make infant feeding decisions, including returning to work and pressures from family members. Despite improved breastfeeding policies, restoring confidence in health workers to support breastfeeding remains a challenge. The post-natal period, when mothers experience breastfeeding difficulties, is particularly critical, and our findings reinforce the importance of continuity of care between communities and health facilities. This research has implications for how health workers are trained to support breastfeeding. Greater attention is needed on developing skills and confidence in identifying, assessing, and supporting women experiencing breastfeeding challenges.

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.

MAIT cells, TCR γδ+ cells and ILCs cells in human breast milk and blood from HIV infected and uninfected women.

BACKGROUND: Human breast milk cells remain poorly characterized for the presence of unconventional T lymphocytes and innate lymphoid cells (ILCs). METHODS: Early breast milk was collected from eight HIV-uninfected and 11 HIV-infected women 3-12 days after delivery. Mucosal-associated invariant T cells (MAIT cells), TCR γδ cells, and innate lymphoid cells (ILCs) were analyzed in breast milk and paired blood samples. RESULTS: CD161+/TRAV1-2 + MAIT cells were detected in breast milk, accounting for a median (IQR) of 0.08% (0.06-0.16) and 0.17% (0.16-0.31) of CD45+ breast milk cells in HIV-uninfected and HIV-infected women, respectively. A selective compartmentalization of γδ T lymphocytes was observed in breast milk. Median (IQR) frequency of γδ T lymphocytes was 8.95% (8.64-12.14) among breast milk lymphocyte cells compared to 2.54% (1.81-4.10) in blood (P = 0.03) in HIV-uninfected women, and 7.26% (4.22-10.54) in breast milk versus 3.31% (2.54-3.80) in blood (P = 0.004) from HIV-infected women. The proportion of group 1 ILC (ILC1) among total ILCs was higher in breast milk compared to blood in HIV-uninfected women (P = 0.03) and HIV-infected women (P = 0.001). The frequency of ILC2 among total ILCs tends to be lower in breast milk compared to blood in HIV-uninfected women (P = 0.06) and HIV-infected women (P = 0.03). CONCLUSION: Unconventional T cells and ILCs that may be involved in both the protection against infection of the lactating mammary gland and maturation of infant's gut and microbiomes account for a detectable fraction of breast milk cells.

A systematic literature review of reported challenges in health care delivery to migrants and refugees in high-income countries - the 3C model.

BACKGROUND: Migrants and refugees have important health needs and face inequalities in their health status. Health care delivery to this patient group has become a challenging public health focus in high income countries. This paper summarizes current knowledge on health care delivery to migrants and refugees in high-income countries from multiple perspectives. METHODS: We performed a systematic literature review including primary source qualitative and quantitative studies between 2000 and 2017. Articles were excluded if the study setting was in low- or middle-income countries or focused on skilled migration. Quality assessment was done for qualitative and quantitative studies separately. Predefined variables were extracted in a standardized form. Authors were approached to provide missing information. RESULTS: Of 185 identified articles, 35 were included in the final analysis. We identified three main topics of challenges in health care delivery: communication, continuity of care and confidence. All but one study included at least one of the three main topics and in 21/35 (60%) all three topics were mentioned. We further developed the 3C model and elaborated the interrelatedness of the three topics. Additional topics identified showed that the specific regional context with legal, financial, geographical and cultural aspects is important and further influences the 3C model. CONCLUSIONS: The 3C model gives a simple and comprehensive, patient-centered summary of key challenges in health care delivery for refugees and migrants. This concept is relevant to support clinicians in their day to day practice and in guiding stakeholders in priority setting for refugee and migrant health policies.

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

In the original publication of this article [1], an author's name needs to be revised from Jacob Creswel to Jacob Creswell.

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.