Effect of injectable progestin-only contraceptives, depot medroxyprogesterone acetate and norethisterone enanthate, on cytokine production during T-cell activation.

PROBLEM: There is paucity of human data about the effects of depot medroxyprogesterone (DMPA) and norethisterone enanthate (Net-En) use on systemic immune function, which may have implications for reproductive tract infection susceptibility and transmissibility. We sought to evaluate the impact of injectable contraceptive use on T-cell responsiveness using T cells exposed in vivo and tested ex vivo. METHODS: Peripheral blood mononuclear cells were obtained from healthy, HIV-negative women after 30, 90 and 180 days of DMPA, norethisterone enanthate (Net-En) or copper intrauterine device (Cu-IUD) contraceptive use. Cells were stimulated ex vivo with phorbol myristate acetate and ionomycin, stained and analysed using flow cytometry. Mixed-effects linear models were used to evaluate change in proportions of T cells producing IFN-γ, TNF-α, IL-4 and IL-13. RESULTS: Compared with baseline, decreased proportions of IFN-γ-producing CD4+ and CD8+ T cells (p = .003, p = .006, respectively) and TNF-α-producing CD4+ and CD8+ T cells (p = .039, p = .034, respectively) were observed after 180 days of DMPA use. Decreased IL-4-producing CD4+ and CD8+ T cells (p = .045 and p = .024, respectively) were noted after 180 days of Net-En use. Decreased IL-4-producing CD4+ T cells were observed after 30 days (p = .035) and not after 180 days of DMPA use (p = .49). There were no changes in proportion of T cells producing IL-13 in DMPA users, nor any changes in IFN-γ, TNF-α and IL-13 in Net-En and Cu-IUD users. CONCLUSION: In vivo exposure of CD4+ and CD8+ T cells to typical pharmacologic concentrations of DMPA does not cause broad suppression to stimuli; however, depletion of specific cytokine-producing T cells may occur after prolonged DMPA use.

Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.

PROBLEM: Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En). METHOD OF STUDY: Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4). RESULTS: Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline. CONCLUSION: Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.

Does supportive legislation guarantee access to pregnancy termination and postabortion care services? Findings from a facility census in Central Province, Zambia.

INTRODUCTION: Zambia is one of the few countries in Africa to permit termination of pregnancy (TOP) on a wide range of grounds. However, substantial barriers remain to TOP and postabortion care (PAC). METHODS: We conducted a census of 153 facilities between March and May 2016. We defined facilities according to whether they met basic and/or comprehensive signal functions criteria for TOP and PAC. We linked our facility data to census data to estimate geographic accessibility under different policy scenarios. RESULTS: Overall, 16% of facilities reported they had performed a TOP and 39% performed a PAC in the last year. Facilities were twice as likely to use medical methods for TOP compared with surgical methods, and four times more likely for PAC. Considerably more facilities had performed TOP or PAC than met the basic or comprehensive signal functions criteria, indicating services were being performed in facilities below essential quality standards. Under current Zambian law for non-emergency scenarios, 21% of women in Central Province lived within 15 km of a facility with basic capability to provide TOP; if midlevel providers were trained to provide TOP, this would increase to 36%. CONCLUSION: A supportive legislative framework is essential, but not in itself sufficient, for adequate access to services. Training midlevel providers, in line with WHO guidance, and ensuring equipment is available in primary care can increase accessibility of TOP and PAC. While both medical and surgical methods need to be available, medical abortion is a safe and effective method that can be provided in low-resource settings.

Setting the research agenda for induced abortion in Africa and Asia.

Provision of safe abortion is widely recognized as vital to addressing the health and wellbeing of populations. Research on abortion is essential to meet the UN Sustainable Development Goals. Researchers in population health from university, policy, and practitioner contexts working on two multidisciplinary projects on family planning and safe abortion in Africa and Asia were brought together for a workshop to discuss the future research agenda on induced abortion. Research on care-seeking behavior, supply of abortion care services, and the global and national policy context will help improve access to and experiences of safe abortion services. A number of areas have potential in designing intervention strategies, including clinical innovations, quality improvement mechanisms, community involvement, and task sharing. Research on specific groups, including adolescents and young people, men, populations affected by conflict, marginalized groups, and providers could increase understanding of provision, access to and experiences of induced abortion. Methodological and conceptual advances, for example in the measurement of induced abortion incidence, complications, and client satisfaction, conceptualizations of induced abortion access and care, and methods for follow-up of patients who have induced abortions, will improve the accuracy of measurements of induced abortion, and add to understanding of women's experiences of induced abortions and abortion care.

DC-SIGN and DC-SIGNR genetic diversity among different ethnic populations: potential implications for pathogen recognition and disease susceptibility.

Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and DC-SIGNR are C-type lectins that serve both as cell adhesion and pathogen recognition receptors. Because of the essential role of the these molecules in the immune response, the implication of their alleles in human disease states, and the possible genetic variation at these loci among ethnically diverse populations, we undertook a study to analyze the full extent of DC-SIGN and DC-SIGNR polymorphisms in Caucasian Canadian and indigenous African populations. We report several novel nucleotide variants within regulatory 5'- and 3'-untranslated regions of the genes that could affect their transcription and translation. There were significant differences in the distribution of DC-SIGN and DC-SIGNR alleles among African and non-African populations. Finally, our study clearly demonstrates that Africans show greater genetic diversity at these two closely-related immune loci than observed in other major population groups. The differences may reflect evolutionary pressures generated by environmental factors, such as prevalent pathogens in these geographically distinct regions. Further studies will be needed to determine the net impact of DC-SIGN and DC-SIGNR genetic variants on the expression, translation, and function of the proteins and to understand how these functional polymorphisms may affect immune responses or immune escape.