Complement Activation in Placental Malaria

Sixty percent of all pregnancies worldwide occur in malaria endemic regions. Pregnant women are at greater risk of malaria infection than their non-pregnant counterparts and have a higher risk of adverse birth outcomes including low birth weight resulting from intrauterine growth restriction and/or preterm birth. The complement system plays an essential role in placental and fetal development as well as the host innate immune response to malaria infection. Excessive or dysregulated complement activation has been associated with the pathobiology of severe malaria and with poor pregnancy outcomes, dependent and independent of infection. Here we review the role of complement in malaria and pregnancy and discuss its part in mediating altered placental angiogenesis, malaria-induced adverse birth outcomes, and disruptions to the in utero environment with possible consequences on fetal neurodevelopment. A detailed understanding of the mechanisms underlying adverse birth outcomes, and the impact of maternal malaria infection on fetal neurodevelopment, may lead to biomarkers to identify at-risk pregnancies and novel therapeutic interventions to prevent these complications

Recreational Diving Impacts on Coral Reefs and the Adoption of Environmentally Responsible Practices within the SCUBA Diving Industry

Recreational diving on coral reefs is an activity that has experienced rapidly growing levels of popularity and participation. Despite providing economic activity for many developing coastal communities, the potential role of dive impacts in contributing to coral reef damage is a concern at heavily dived locations. Management measures to address this issue increasingly include the introduction of programmes designed to encourage environmentally responsible practices within the dive industry. We examined diver behaviour at several important coral reef dive locations within the Philippines and assessed how diver characteristics and dive operator compliance with an environmentally responsible diving programme, known as the Green Fins approach, affected reef contacts. The role of dive supervision was assessed by recording dive guide interventions underwater, and how this was affected by dive group size. Of the 100 recreational divers followed, 88 % made contact with the reef at least once per dive, with a mean (±SE) contact rate of 0.12 ± 0.01 per min. We found evidence that the ability of dive guides to intervene and correct diver behaviour in the event of a reef contact decreases with larger diver group sizes. Divers from operators with high levels of compliance with the Green Fins programme exhibited significantly lower reef contact rates than those from dive operators with low levels of compliance. The successful implementation of environmentally responsible diving programmes, which focus on influencing dive industry operations, can contribute to the management of human impacts on coral reefs

Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV

Background Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings. Objective We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy. Study Design This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda. Pregnant women living with HIV were enrolled between 12-28 weeks of gestation. Plasma samples were evaluated for angiogenic biomarkers (angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin) by enzyme-linked immunosorbent assay between: 16-<20, 20-<24, 24-<28, 28-<32, 32-<36, 36-<37 weeks of gestation. The primary outcome was preterm birth. Results In all, 1115 plasma samples from 326 pregnant women and adolescents were evaluated. There were no differences in angiogenic factors according to antiretroviral therapy group (P > .05 for all). The incidence of adverse birth outcomes was 16.9% for spontaneous preterm births, 25.6% for small-for-gestational-age births, and 2.8% for stillbirth. We used linear mixed effect modelling to evaluate longitudinal changes in angiogenic factor concentrations between birth outcome groups adjusting for gestational age at venipuncture, maternal age, body mass index, gravidity, and the interaction between treatment arm and gestational age. Two angiogenic factors–soluble endoglin and placental growth factor–were associated with adverse birth outcomes. Significantly higher concentrations of soluble endoglin throughout gestation were found in study participants destined to deliver preterm [likelihood ratio test, χ2(1) = 12.28, P < .0005] and in those destined to have stillbirths [χ2(1) = 5.67, P < .02]. By contrast, significantly lower concentrations of placental growth factor throughout gestation were found in those destined to have small-for-gestational-age births [χ2(1) = 7.89, P < .005] and in those destined to have stillbirths [χ2(1) = 21.59, P < .0001]. Conclusion An antiangiogenic state in the second or third trimester is associated with adverse birth outcomes, including stillbirth in women and adolescents living with HIV and receiving antiretroviral therapy

Host Biomarkers Are Associated With Response to Therapy and Long-Term Mortality in Pediatric Severe Malaria.

Background. Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions.Methods. This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria. One hundred eighty children aged 1–10 years were enrolled at Jinja Regional Referral Hospital in Uganda and followed for up to 6 months.Results. There were no differences between the 2 study arms in the rate of biomarker recovery. Median levels of Ang-2, CXCL10, and sFlt-1 were higher at admission in children who died in-hospital (n = 15 of 180; P < .001, P = .027, and P = .004, respectively). Elevated levels of Ang-2, sTREM-1, CXCL10, and sICAM-1 were associated with prolonged clinical recovery times in survivors. The Ang-2 levels were also associated with postdischarge mortality (P < .0001). No biomarkers were associated with neurodisability.Conclusions. Persistent endothelial activation and dysfunction predict survival in children admitted with severe malaria

Inflammatory and Angiogenic Factors at Mid-Pregnancy Are Associated with Spontaneous Preterm Birth in a Cohort of Tanzanian Women.

Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB).\ud Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12-27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA. In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile. Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies

"Surviving discrimination by pulling together" : LGBTQI cancer patient and carer experiences of minority stress and social support

Background: Lesbian, gay, bisexual, transgender, queer and/or intersex (LGBTQI) people with cancer and their carers report poorer psychological outcomes than the general non-LGBTQI cancer population. There is growing acknowledgement that these health inequities can be explained by minority stress, which can be buffered by social support. Study Aim: To examine subjective experiences of minority stress and social support for LGBTQI people with cancer and their carers, drawing on qualitative findings from the Out with Cancer study. Method: An online survey including open ended items was completed by 430 LGBTQI cancer patients and 132 partners and other carers, representing a range of tumor types, sexual and gender identities, age and intersex status. A sub-sample of 104 patients and 31 carers completed an interview, with a follow-up photovoice activity and second interview completed by 45 patients and 10 carers. Data was thematically analysed using an intersectional theoretical framework. Results: Historical and present-day experiences of discrimination, violence, family rejection and exclusion created a legacy of distress and fear. This impacted on trust of healthcare professionals and contributed to distress and unmet needs in cancer survivorship and care. Social support, often provided by partners and other chosen family, including intimate partners and other LGBTQI people, buffered the negative impacts of minority stress, helping LGBTQI patients deal with cancer. However, some participants lacked support due to not having a partner, rejection from family of origin and lack of support within LGBTQI communities, increasing vulnerability to poor psychological wellbeing. Despite the chronic, cumulative impacts of minority stress, LGBTQI patients and carers were not passive recipients of discriminatory and exclusion in cancer care, demonstrating agency and resistance through collective action and advocacy. Conclusion: LGBTQI people have unique socio-political histories and present-day psycho-social experiences that contribute to distress during cancer. Social support serves to buffer and ameliorate this distress. There is a need for cancer healthcare professionals and support services to be aware of and responsive to these potential vulnerabilities, including the intersectional differences in experiences of minority stress and social support. There is also a need for recognition and facilitation of social support among LGBTQI people with cancer and their carers

LGBTQI cancer patients' quality of life and distress : a comparison by gender, sexuality, age, cancer type and geographical remoteness

Background: There is growing acknowledgement of the psycho-social vulnerability of lesbian, gay, bisexual, transgender, queer and/or intersex (LGBTQI) people with cancer. The majority of research to date has focused on cisgender adults with breast or prostate cancer. Study Aim: This study examined psycho-social factors associated with distress and quality of life for LGBTQI cancer patients and survivors, across a range of sexualities and gender identities, intersex status, tumor types, ages and urban/ rural/remote location using an intersectional theoretical framework. Method: 430 LGBTQI people with cancer completed an online survey, measuring distress, quality of life (QOL), and a range of psycho-social variables. Participants included 216 (50.2%) cisgender women, 145 (33.7%) cisgender men, and 63 (14.7%) transgender and gender diverse (TGD) people. Thirty-one (7.2%) participants reported intersex variation and 90 (20%) were adolescents or young adults (AYA), aged 15-39. The majority lived in urban areas (54.4%) and identified as lesbian, gay or bisexual (73.7%), with 10.9% identifying as bisexual, and 10.5% as queer, including reproductive (32.4%) and non-reproductive (67.6%) cancers. Results: Forty-one percent of participants reported high or very high distress levels, 3-6 times higher than previous non-LGBTQI cancer studies. Higher rates of distress and lower QOL were identified in TGD compared to cisgender people, AYAs compared to older people, those who identify as bisexual or queer, compared to those who identify as lesbian, gay or homosexual, and those who live in rural or regional areas, compared to urban areas. Elevated distress and lower QOL was associated with greater minority stress (discrimination in life and in cancer care, discomfort being LGBTQI, lower outness) and lower social support, in these subgroups. There were no differences between reproductive and non-reproductive cancers. For the whole sample, distress and poor QOL were associated with physical and sexual concerns, the impact of cancer on gender and LGBTQI identities, minority stress, and lack of social support. Conclusion: LGBTQI people with cancer are at high risk of distress and impaired QOL. Research and oncology healthcare practice needs to recognize the diversity of LGBTQI communities, and the ways in which minority stress and lack of social support may affect wellbeing

Attitudes, knowledge and practice behaviours of oncology health care professionals towards lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) patients and their carers : a mixed-methods study

Objective: There is growing recognition that health care professionals (HCPs) and policy makers are insufficiently equipped to provide culturally competent care to lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) cancer patients and their families. We examined HCP attitudes, knowledge, and practices regarding LGBTQI cancer care using a mixed-methods research design. Method: Surveys were completed by 357 oncology HCPs in nursing (40%), medical (24%), allied health (19%), and clinical leadership roles (11%); 48 of the surveyed HCPs were interviewed. Results: Most HCPs reported being comfortable treating LGBTQI patients, but reported low levels of confidence and knowledge and systemic barriers to LGBTQI cancer care. Most wanted more education and training, particularly on trans and gender-diverse people (TGD) and those born with intersex variations. Conclusion: Education of HCPs and health system changes are required to overcome barriers to the provision of culturally competent cancer care for LGBTQI patients. Practice implications: These findings reinforce the need for inclusion of LGBTQI content in HCP education and professional training curricula, and institutional support for LGBTQI-inclusive practice behaviours. This includes administrative and visual cues to signal safety of LGBTQI patients within cancer care, facilitating inclusive environments, and the provision of tailored patient-centred care

LGBTQI inclusive cancer care : a discourse analytic study of health care professional, patient and carer perspectives

Background: Awareness of the specific needs of LGBTQI cancer patients has led to calls for inclusivity, cultural competence, cultural safety and cultural humility in cancer care. Examination of oncology healthcare professionals’ (HCP) perspectives is central to identifying barriers and facilitators to inclusive LGBTQI cancer care. Study Aim: This study examined oncology HCPs perspectives in relation to LGBTQI cancer care, and the implications of HCP perspectives and practices for LGBTQI patients and their caregivers. Method: 357 oncology HCPs in nursing (40%), medical (24%), allied health (19%) and leadership (11%) positions took part in a survey; 48 HCPs completed an interview. 430 LGBTQI patients, representing a range of tumor types, sexual and gender identities, age and intersex status, and 132 carers completed a survey, and 104 LGBTQI patients and 31 carers undertook an interview. Data were analysed using thematic discourse analysis. Results: Three HCP subject positions – ways of thinking and behaving in relation to the self and LGBTQI patients – were identified:’Inclusive and reflective’ practitioners characterized LGBTQI patients as potentially vulnerable and offered inclusive care, drawing on an affirmative construction of LGBTQI health. This resulted in LGBTQI patients and their carers feeling safe and respected, willing to disclose sexual orientation and gender identity (SOGI) status, and satisfied with cancer care. ‘Egalitarian practitioners’ drew on discourses of ethical responsibility, positioning themselves as treating all patients the same, not seeing the relevance of SOGI information. This was associated with absence of LGBTQI-specific information, patient and carer anxiety about disclosure of SOGI, feelings of invisibility, and dissatisfaction with healthcare. ‘Anti-inclusive’ practitioners’ expressed open hostility and prejudice towards LGBTQI patients, reflecting a cultural discourse of homophobia and transphobia. This was associated with patient and carer distress, feelings of negative judgement, and exclusion of same-gender partners. Conclusion: Derogatory views and descriptions of LGBTQI patients, and cis-normative practices need to be challenged, to ensure that HCPs offer inclusive and affirmative care. Building HCP’s communicative competence to work with LGBTQI patients needs to become an essential part of basic training and ongoing professional development. Visible indicators of LGBTQI inclusivity are essential, alongside targeted resources and information for LGBTQI people