Combination of serological and cytokine release assays for improved diagnosis of childhood tuberculosis in Zambia (PROMISE-TB).

Objectives: The diagnostic gaps for childhood tuberculosis (TB) remain considerable in settings with high TB incidence and resource constraints. We established and evaluated the performance of a scoring system based on a combination of serological tests and T-cell cytokine release assays, chosen for their ability to detect immune responses indicative of TB, in a context of high prevalence of pediatric HIV infection.

Methods: We enrolled 628 consecutive children aged ≤15 years, admitted for TB suspicion.

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.

Evaluation of the prevention of mother-to-child transmission of HIV programs at the second immunization visit in Burkina Faso and Zambia.

Objective: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6-8 weeks.

Design: This was a cross sectional study.

Methods: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions.

Facilitators and barriers to infant post-natal HIV prophylaxis, a qualitative sub-study of the PROMISE-EPI trial in Lusaka, Zambia.

Background: Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL.

Impact of the COVID-19 Pandemic on Tuberculosis Testing and Treatment at a Tertiary Hospital in Zambia.

Globally, tuberculosis (TB) testing and treatment have declined dramatically during the COVID-19 pandemic. We quantified the change in TB visits, testing, and treatment compared with a 12-month pre-pandemic baseline at the national referral hospital's TB Clinic in Lusaka, Zambia, in the first year of the pandemic. We stratified the results into early and later pandemic periods.

Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV.

HIV-exposed uninfected (HEU) children show impaired health outcomes during childhood. A high rate of mitochondrial DNA (mtDNA) instability was reported in the blood of HEU at birth. We aimed to explore the relationship between these health outcomes and mtDNA deletions over time in a case series of 24 HEU children.

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.

Feasibility of using infant testing during immunization to estimate HIV mother-to-child-transmission rates in Zambia.

Background: This study piloted the feasibility of infant testing in immunization services as a strategy for estimating MTCT rates among the population of HIV exposed infants at national and subnational levels in Zambia.

Methods: The study recruited a cross-sectional nationally representative sample of 8042 caregiver-baby pairs in 38 high volume immunization sites in 7 towns across 3 provinces of Zambia. All mothers who brought their children below the age of one year for immunization at the study facilities were invited to participate in the study.

A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).

Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory).

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction.

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 ( = 32), which was compared with healthy controls ( = 15).

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants.

The CD133 Stem/Progenitor-Like Cell Subset Is Increased in Human Milk and Peripheral Blood of HIV-Positive Women.

Human milk is a significant source of different CD133 and/or CD34 stem/progenitor-like cell subsets in healthy women but their cell distribution and percentages in this compartment of HIV-positive women have not been explored. To date, a decrease of CD34 hematopoietic stem and progenitor cell frequencies in peripheral blood and bone marrow of HIV-positive patients has been reported. Herein, human milk and peripheral blood samples were collected between day 2-15 post-partum from HIV-positive and HIV-negative women, and cells were stained with stem cell markers and analyzed by flow cytometry.

Relationships Between Maternal Antibody Responses and Early Childhood Infection With Kaposi Sarcoma-Associated Herpesvirus.

While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.

Healthy pregnancies and essential fats: focus group discussions with Zambian women on dietary need and acceptability of a novel RUSF containing fish oil DHA.

Background: Nut butter-based Ready to Use Supplemental Foods (RUSF) are an effective way to add nutrients and calories to diets of malnourished and food insecure populations. The RUSF formulations have been further modified to add micronutrients including iron and folic acid needed during pregnancy and lactation. Because docosahexaenoic acid (DHA, C22:6 n-3) enhances fetal development and birth outcomes, it has been suggested that perhaps RUSF formulations for pregnancy should also include this Omega 3 fatty acid.

Large Stem/Progenitor-Like Cell Subsets can Also be Identified in the CD45 and CD45 Populations in Early Human Milk.

Background: Stem/progenitor cells have been identified in human milk. However, characterization and percentages of cell subsets in human milk using hematopoietic stem and progenitor cell markers according to the differential expression of CD45, i.e.

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.

Growth in HIV-1-exposed but uninfected infants treated with lopinavir-ritonavir versus lamivudine: a secondary analysis of the ANRS 12174 trial.

Background: The tolerance of antiretroviral drugs in infants must be carefully evaluated. In previous studies of children with HIV type 1 (HIV-1) less weight gain was observed in children given lopinavir-ritonavir-based combinations than those given nevirapine. We aimed to compare the effects of lopinavir-ritonavir and lamivudine on growth in HIV-exposed uninfected infants included in the ANRS 12174 trial.

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.

Human papillomavirus (HPV) shedding in breast milk from African women living with HIV.

Background: Little is known about human papillomavirus (HPV) shedding in human breast milk.

Objective: To investigate HPV shedding in mature breast milk specimens collected from breastfeeding African women living with HIV-1 and not receiving antiretroviral treatment.

Design: 62 African women enrolled in the ANRS 12174 trial participated in this study.