Publications by authors named "Happel A"

Objectives: Human papillomavirus (HPV) is the leading cause of cervical cancer, with adolescent girls and young women (AGYW) in sub-Saharan Africa carrying a disproportionately high burden of infection. Hormonal contraceptives may influence HPV acquisition, persistence, and clearance, but evidence remains inconclusive. This sub-study aimed to evaluate the impact of different hormonal contraceptives on HPV prevalence and genotype distribution in AGYW.

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Purpose Of Review: Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated.

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Article Synopsis
  • Depletion of species in the vaginal tract leads to bacterial vaginosis (BV), which is linked to poor reproductive health and higher risk of STIs; current antibiotic treatments have low success rates.
  • A study conducted in Cape Town explored blood donors' knowledge and attitudes toward vaginal microbiota transplantation (VMT) as a potential alternative treatment for BV through a questionnaire.
  • Results showed a significant majority (86%) of women were open to donating vaginal samples, with willingness increased by a belief in helping others and prior knowledge of healthy vaginal microbiomes; concerns about discomfort and embarrassment affected those unwilling to donate.
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Objective: Human papillomavirus (HPV) vaccines and DNA testing roll out in resource-constrained settings. We evaluated the natural history of HPV infections in African women to contribute to normative guidance.

Methods: Women aged 16 to 35 years were enrolled from 3 sites in South Africa and Kenya and followed quarterly for 18 months.

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Some studies have reported increased infectious morbidity and all-cause mortality risk among infants HIV-exposed uninfected compared with infants HIV-unexposed uninfected. In a retrospective analysis of infants enrolled in the Botswana-based Tshilo Dikotla study, we found no difference in the prevalence of infectious hospitalizations or deaths from any cause in the first year of life by perinatal HIV exposure.

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  • The Landscape Theory of Food Web Architecture (LTFWA) explores how body size, trophic position, and energy channels interconnect in diverse habitats to maintain system stability, but evidence has been inconsistent across different ecosystems.
  • In a study of the Lake Michigan food web, researchers found a positive correlation between body size and trophic position, with variations based on whether species were supported by pelagic or benthic energy sources.
  • The findings indicated that while native top predators contribute to food web stability by connecting energy pathways, introduced species may disrupt this structure, highlighting the complex impacts of human activity on ecosystem dynamics.
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Infants who are HIV exposed but uninfected (iHEU) have higher risk of viral infections compared to infants who are HIV unexposed (iHUU). We explored the effect of intrauterine HIV exposure on the infant antibody repertoire by quantifying plasma immunoglobulin (Ig) G against 206 eukaryote-infecting viruses using phage immunoprecipitation sequencing (PhiPSeq) in iHEU and iHUU at birth and 36 weeks of life. Maternal HIV infection altered the infant IgG repertoire against eukaryote-infecting viruses at birth, resulting in significantly lower antibody breadth and diversity among iHEU compared to iHUU.

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  • Infants exposed to HIV but uninfected (iHEU) show a higher risk of infections compared to unexposed infants (iHUU), potentially due to differences in immune response related to their gut microbiota.
  • In a study of 278 infants from South Africa and Nigeria, researchers found that geographic location and age significantly influenced gut microbiota composition rather than HIV exposure.
  • The study concluded that while HIV exposure had minimal impact on gut microbiota, certain gut microbes and HIV exposure were independently linked to the effectiveness of tetanus vaccine responses in infants.
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Bacille Calmette-Guerin (BCG) vaccine can elicit good T1 responses in neonates. We hypothesized that the pioneer gut microbiota affects vaccine T cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination.

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Article Synopsis
  • Recent studies suggest that data on non-barrier contraceptives and the mucosal microbiome has often been confounded by behavioral factors, leading to potential biases in previous observational studies.
  • This review highlights evidence from randomized trials, indicating that long-acting progestin-only contraceptives and oral contraceptive pills (OCPs) generally have little to no impact on the vaginal microbiome or the risk of bacterial STIs, while some evidence ties copper IUDs to an increased risk of bacterial vaginosis.
  • The conclusion stresses the need for thorough evaluations of different hormonal contraceptives and their biological effects on the microbiome to enhance family planning options and guidance.
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Introduction: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses.

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Article Synopsis
  • Infants exposed to HIV, but uninfected (iHEU), have a higher risk of infections compared to those unexposed (iHUU), with potential links to gut microbiota influencing immune development.
  • A study involving 278 infants in South Africa and Nigeria assessed gut microbiota and responses to the tetanus toxoid (TT) vaccine, showing that geographical location and age had a greater impact than HIV exposure itself.
  • The results revealed that while HIV exposure had a minimal effect on gut microbiota changes over time, it and specific gut microbes independently predicted how well infants responded to the vaccine at 15 weeks.
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Cesarean section rates continue to rise globally, and C-sectioned infants are at a higher risk of adverse child outcomes. In this issue of Cell Host & Microbe, Zhou et al. report that vaginal microbial transfer (VMT) from birth mother to infant post-delivery may alter infant gut microbiota and improve neurodevelopment.

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Article Synopsis
  • - The review highlights concerns about the potential effects of the contraceptive DMPA-IM on the female genital tract, particularly regarding the risk of HIV infection among cisgender women in Africa.
  • - Previous studies indicated that DMPA-IM users exhibited higher levels of bacterial vaginosis, inflammation, and changes in cervical health, raising worries about STI risks.
  • - However, findings from the ECHO Trial suggest that DMPA-IM does not negatively impact vaginal health or increase STI risk, indicating it can be considered safe for women at high risk of STIs, including HIV.
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Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9-18 months using T-SPOT.TB.

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The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15-19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex).

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Floating Treatment Wetlands (FTWs) are an emerging ecological engineering technology being applied the restoration of eutrophic urban water bodies. Documented water-quality benefits of FTW include nutrient removal, transformation of pollutants, and reduction in bacterial contamination. However, translating findings from short-duration lab and mesocosm scale experiments, into sizing criteria that might be applied to field installations is not straightforward.

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Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays.

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Article Synopsis
  • There is a lack of comprehensive genome sequences for various viruses found in the female genital tract, except for papillomaviruses.
  • This study presents the genome sequences of multiple types of viruses, including 16 microviruses, 3 anelloviruses, 2 polyomaviruses, 1 genomovirus, and 1 caudovirus.
  • The identified viruses were sourced from vaginal secretion samples collected from adolescents in South Africa.
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Hormonal contraceptives (HCs) are vital in managing the reproductive health of women. However, HC usage has been linked to perturbations in cervicovaginal immunity and increased risk of sexually transmitted infections. Here, we evaluated the impact of three HCs on the cervicovaginal environment using high-throughput transcriptomics.

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Article Synopsis
  • - Several soluble cytokines linked to cervicovaginal inflammation and non-ideal vaginal microbiota may increase HIV risk and are used in preclinical tests for vaginal products.
  • - There are no established biomarkers for assessing the safety of new vaginal products in clinical trials, making it difficult to effectively evaluate these products before human testing.
  • - The review aimed to identify and recommend methods for selecting and measuring immune markers that can help ensure the safety of novel vaginal products in early human trials.
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Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guérin (BCG) vaccination in a cohort of HIV-exposed, uninfected and HIV-unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day 1, and 7, 15, and 36 weeks of life.

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Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry).

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Background: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls).

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